Datasets:

YBXL

/

pubmed

like 1

8221030

Involvement of free radicals in ageing: a consequence or cause of senescence.

Free oxygen radicals are increasingly discussed as important factors involved in the phenomenon of biological ageing. Higher formation rates of free radicals from senescent animals observed in isolated biological materials (mainly in mitochondria), accumulation of free radical damage and changes of antioxidant capacities appear to prove the correctness of this assumption. In the present review these findings are critically examined in order to evaluate whether free radicals do contribute to the initiation and/or propagation of ageing. It is concluded that data available so far do not allow a definite answer to this question although, free radicals are very likely to contribute considerably to the development of stochastic disorders observed during the progress of ageing.

Aging,Animals,Free Radicals,Homeostasis,Humans,Lipid Peroxidation,Mitochondria,Oxidation-Reduction,Oxygen,Reactive Oxygen Species,Superoxide Dismutase

4328,203456,513850,629999,710436,1270774,1650737,2055497,2072821,2283087,2546868,2552230,2684796,2746659,2981404,3032683,3034677,3036875,3691507,3835415,3982084,4346473,4737333,5389100,6309165,6592579,7010357,7271862,7412499,13332224

8221031

Free radical disorders of preterm infants.

In recent years increasing experimental and clinical data have provided compelling evidence for the involvement of oxygen free radicals in the 3 main disorders of prematurity--chronic lung disease, retinopathy of prematurity and intraventricular haemorrhage. Infants born prior to 30 weeks gestation or weighing less than 1500 g at birth appear to be most at risk. They are very underdeveloped and as a consequence of the immaturity of their lungs often require intense respiratory support, including the provision of supplemental oxygen. The theoretical basis for free radical involvement in these disorders is that oxygen centred radicals and related reactive oxygen metabolites are formed too rapidly to be detoxified by the antioxidant defence mechanisms in specific tissues. In the case of chronic lung disease, the evidence currently favours excess oxygen (hyperoxia) as the cause of the greater oxygen free radical production, whereas in retinopathy of prematurity and intraventricular haemorrhage, it is proposed that low oxygen tensions (hypoxia) followed by periods of reoxygenation is the more likely stimulus for excess radical formation.

Bronchopulmonary Dysplasia,Cerebral Hemorrhage,Cerebral Ventricles,Endothelium,Free Radicals,Humans,Infant, Newborn,Infant, Premature,Lung,Oxygen,Reactive Oxygen Species,Retinopathy of Prematurity

355877,385819,490265,579984,622396,691070,702245,710594,739764,1250644,2013272,2230537,3277672,3565601,3756211,3900846,4022676,4988417,5334613,5389100,6089081,6112419,6122890,6263743,6291460,6299175,6407714,6504632,6548176,6688950,6697450,6728556,6738695,6892851,6894488,6897110,6959554,7029275,7045320,7271862,7287745,13156638

8221032

Prospects for the prevention of free radical disease, regarding cancer and cardiovascular disease.

Free radicals may be involved in the aetiology of cancer and cardiovascular diseases. In epidemiological studies poor plasma levels of all essential antioxidants are associated with increased relative risks; in particular, low levels of carotene and vitamin E with the risk of cancer and ischemic heart disease, respectively. The studies suggest that for optimal synergistic protection the plasma antioxidant levels should simultaneously exceed the threshold values of 28-30 mumol/l lipid-standardized vitamin E, 40-50 mumol/l vitamin C, 0.4-0.5 mumol/l carotene and 2.2-2.8 mumol/l lipid-standardized vitamin A. However the preventive efficacy of an optional antioxidant status is still to be proven in randomized intervention trials. Although these antioxidant micronutrients may be the primary protective components of vegetable-rich 'preventive' diets, the potentials of other plant components await exploration, eg carotenoids other than beta-carotene, bioflavonoids and oxygen-sensitive B-vitamins.

Adult,Antioxidants,Cardiovascular Diseases,Case-Control Studies,Diet,Female,Humans,Male,Middle Aged,Neoplasms,Prospective Studies

1311987,1349935,1351549,1531683,1536130,1541796,1591317,1591855,1637180,1637852,1652140,1670647,1756027,1775382,1877596,1878353,1884464,1985387,1985393,1985394,1985395,1985396,1985398,1985402,1985403,1985406,1985410,2000375,2017400,2021143,2088799,2117596,2162153,2202901,2216898,2239900,2258274,2338463,2342127,2375783,2507701,2648148,2731108,2981433,3038299,3192329,3202092,3258519,3276161,3304060,3375778,3390380,3403123,3475994,3495167,3497600,3510621,3574421,3620319,3666521,3773937,3812345,3918611,3986777,6351251,6537988,6595456,6704307

8221033

Prospects for treatment of free radical-mediated tissue injury.

Toxic metabolites of oxygen are generated normally by aerobic metabolism in cells and this generation can significantly increase in certain pathologic conditions. When endogenous antioxidant defense capabilities are exceeded by this oxidant flux, tissue injury occurs. This process can be intercepted pharmacologically at different levels with agents that scavenge reactive oxygen metabolites, block their generation, or enhance endogenous antioxidant capabilities. In many situations, such as the treatment of post-ischaemic reperfusion injury, efficacy of antioxidant is related primarily to the proportionate magnitude of the total injury sustained that is due to an antioxidant mechanism. This approach has shown great promise in animal models of clinical problems and has been tested successfully in early, controlled clinical trials.

Animals,Antioxidants,Humans,Intestinal Diseases,Intestinal Mucosa,Kidney Transplantation,Reperfusion Injury

217393,1496693,1689516,1798280,1985364,2008110,2050298,2069440,2219352,2335028,2407002,2652409,2966413,2984078,2996556,3020994,3037918,3039675,3278416,3287616,3310486,3631303,3632115,3698229,4007413,6263743,6273253,6309018,6434591,6687872

8221040

Neutrophil chemotaxis in the horse is not mediated by a complex of equine neutrophil elastase and equine alpha-1-proteinase inhibitor.

Studies have demonstrated that as a result of proteolytic inactivation or complex formation (with neutrophil elastase), human alpha-1-proteinase inhibitor (API) becomes a potent chemoattractant for human neutrophils. The present study aimed to investigate the in vitro chemotactic response of equine neutrophils to an equivalent complex of equine API and neutrophil elastase. No evidence of neutrophil migration was observed towards purified complex derived from equine neutrophil elastase and the Spi 1 isoform of equine API, or to crude mixtures of porcine pancreatic elastase and unseparated equine API isoforms, although the same neutrophil preparations actively migrated towards zymosan activated plasma. It was concluded that, in the horse, complexes of API are not involved in the migration of neutrophils to sites of inflammation.

Animals,Cell Movement,Chemotaxis, Leukocyte,Horses,Leukocyte Elastase,Male,Neutrophils,Pancreatic Elastase,alpha 1-Antitrypsin

6008,621166,1645729,1772402,1793458,2006910,2160076,2226400,2619289,3257965,3259253,3494198,3537008,3628984,4568301,5432063,6248959,6540062,7073055,7073083,7371229,13872176

8221045

Silent cerebral embolism caused by neurologically symptomatic high-grade carotid stenosis. Event rates before and after carotid endarterectomy.

Fourteen symptomatic patients with severe extracranial internal carotid artery stenosis (> or = 70% of luminal narrowing) were monitored using long-term transcranial Doppler ultrasonography to determine the rate of clinically silent embolism of the ipsilateral middle cerebral artery. Before carotid endarterectomy (all patients being treated with intravenous heparin), 462 such events occurred during a total monitoring time of 45 h. Statistical analyses of the inter-event intervals and of the relationship between events and cardiac cycle revealed random occurrence. While the ipsilateral events were found in each subject, silent embolism of the contralateral middle cerebral artery occurred in only four patients each of whom had angiographically proven intracranial cross-flow from the symptomatic carotid territory (39 embolic events during 7 h monitoring time). The other 10 patients showed no contralateral embolism (10 h monitoring time). Five or more days (median 10 days) after surgery and cessation of intravenous anticoagulation the ipsilateral event rate had dropped to 13 in 33 h (P < 0.001) and the contralateral rate to zero. This suggests that the stenosed arterial segment is the main source of cerebral embolism detectable with ultrasound in symptomatic patients with high-grade internal carotid stenosis, and that carotid endarterectomy substantially reduces the rate of these events. Since reduction of ipsilateral stroke risk by successful endarterectomy is known to be of a similar degree in patients as those studied here, transcranially detected embolism may represent a new marker of disease activity of extracranial carotid artery stenosis.

Adult,Aged,Carotid Artery, Internal,Carotid Stenosis,Endarterectomy, Carotid,Female,Humans,Intracranial Embolism and Thrombosis,Male,Middle Aged,Ultrasonography

534423,1440714,1675378,1727977,2003290,2042939,2215951,2264082,2408197,2671268,2783342,2783350,2785365,3629646,3632384,5422409,5460773,5953829,6164952,6182861,6362094,6615213,6801822,6824372,7143059,14493108

8221041

The dangers of disease transmission by artificial insemination and embryo transfer.

This review summarizes the major infectious diseases of the three major agricultural species (cattle, sheep and pigs) and horses, and presents the evidence for and against the possibility of infectious agents being transmitted between animals via the venereal route or by the use of semen or early embryos in commercial artificial insemination (AI) or embryo transfer (ET). Cattle feature most prominently in the widespread distribution of frozen semen, and national and international organizations have set out guidelines to work towards disease-free bull studs with semen free from potential pathogens. With the control of major epizootic diseases, attention has been focused on such diseases as IBR, BVD and blue tongue, where clinical signs are rarely evident but the detection of virus in semen is of great importance. New information on the relevance of bacterial disease such as Mycobacterium paratuberculosis, campylobacteriosis and leptospirosis is reviewed, along with details of the mycoplasma and ureaplasma species of the bull's genital tract. Bovine spongiform encephalopathy (BSE) has attracted much research and semen is not regarded as a source of infection. New work on the pathogenesis of a number of diseases and the use of new biotechnology in diagnosis is included. The International Embryo Transfer Society (IETS) has encouraged a great deal of experimental work--much originating in Canada--on the risk of transmission of disease from donors to recipients via a 7-day-old blastocyst. There has been much success in demonstrating that with an approved protocol of handling the embryos, to date there is very little danger in disease transmission with both viruses and bacteria. The mycoplasma group appear more intractable and the role of BSE is still being evaluated. In sheep, scrapie, Brucella ovis infection and blue tongue feature in current work. In the pig there is a surge in international movement of pig semen, and Aujeszky's disease and the new so-called Blue Ear disease feature prominently. Much work is in progress on infectious agents likely to be found in the semen of stallions, with an expanding trade in the international movement of chilled and frozen semen. Equine embryo transfer experiments are hampered by the very limited number of embryos available. Reference is also made to the further risk of disease transmission by in vitro manipulated embryos.

Animal Diseases,Animals,Bacterial Infections,Cattle,Embryo Transfer,Horses,Insemination, Artificial,Risk Factors,Sheep,Swine,Virus Diseases

172055,173847,225719,987101,1347078,1350694,1566539,1617201,1626360,1651960,1654660,1715811,1771755,1847151,1852081,1963771,2107070,2111595,2163996,2175520,2177290,2186676,2298657,2306605,2385913,2402878,2417297,2496889,2537554,2548424,2552646,2556101,2614219,2824772,2830936,2832997,2837113,2837860,2842930,2844043,2845636,2849388,2853175,2989932,2996262,3011714,3206786,3219829,3281337,3354969,3424585,3619343,3629862,3705372,3727326,3750750,3750752,3934838,4013041,4116973,4291335,4293689,4301432,4316060,4422107,4480374,4625088,4727795,5414867,5680978,6093648,6254406,6255663,6282077,6283958,6289508,6289509,6312040,6312854,6318611,6375961,6442027,6798655,6813384,6868320,7024331,7073089,7142533,7263470,7303438,7337908,9210929,14299417,15463161,16725707,16726088,16726134,16726224,16726225,16726257,16726278,16726313,16726352,16726359,16726367,16726381,16726417,16726433,16726479,16726507,16726542,16726604,16726617,16726660,16726710,16726750,16726850,16726896,16726913,16727038,16727166,17422489,17423063,24049903

8221046

Examination of distal involvement in cisplatin-induced neuropathy in man. An electrophysiological and histological study with particular reference to touch receptor function.

Cisplatin is a widely used anti-neoplastic agent with dose-dependent sensory neuropathy as a major side-effect. The mechanism for the neuropathy is poorly understood; it may be caused by a lesion of the dorsal root ganglion cells or by a distal axonopathy. This distinction is important since regeneration in a neuronopathy is impossible, whereas recovery may occur if the axon is affected only distally. The most distal part of the sensory nerve fibre is, however, not accessible for conventional electrophysiological examination. To ascertain whether the distal receptor-associated part of the fibre is involved, we have used a method previously untested in patients with neuropathy. In 26 males treated with cisplatin for testicular cancer 3-6.5 years previously, and in 22 normal males, the compound sensory action potentials evoked by a tactile probe were recorded through needle electrodes placed close to the sural and median nerves. The responses were compared with action potentials evoked by electrical stimulation of the same nerves. Biopsies from the distal sural nerve at the dorsolateral aspect of the foot were obtained in three patients and in four subjects not treated with cisplatin. Sixteen patients had received a conventional dose (307-435 mg/m2) of cisplatin and 10 patients had received a high dose (553-1197 mg/m2). Two-thirds of the conventional dose patients and all the high dose patients had mild to severe sensory loss and reduced or absent tendon reflexes. The amplitude of the electrically evoked sensory action potential decreased with increasing dose of cisplatin and was correlated with the reduction of vibration sense. Tactile responses, probably originating mainly from Pacinian corpuscles, were, with the exception of two high dose patients, recorded from all sural and median nerves. The two high dose patients without a tactile response had a severely reduced or no electrically evoked response at the sural nerve. The sural nerve biopsies from high dose patients showed loss of large fibres; Pacinian corpuscles were obtained in two of these patients and contained normal axons. Our findings do not suggest that cisplatin causes a primarily distal lesion with sparing of more proximal parts of the peripheral nerve. We interpret the results as being consistent with a neuronopathy affecting primarily large sensory neurons. Brainstem and somatosensory evoked potentials and H-reflexes suggested that the spinal cord and brainstem were affected as well.

Action Potentials,Adult,Antineoplastic Agents,Cisplatin,Evoked Potentials, Auditory, Brain Stem,Evoked Potentials, Somatosensory,Humans,Male,Mechanoreceptors,Median Nerve,Middle Aged,Pacinian Corpuscles,Peripheral Nervous System Diseases,Sensation Disorders,Sural Nerve,Touch

81756,164259,207427,228833,389195,439026,458479,702358,1308101,1543351,1557087,1628208,1649397,1658236,2128320,2152972,2275399,2275400,2296357,2355942,2476531,2597994,2761702,2804617,2995600,3003868,3007675,3040462,3185601,3332448,3439842,3668571,3673502,3962607,4039651,4326086,4621505,4759677,4957896,4972033,5032671,5475340,5721757,6088023,6169505,6221191,6280320,6330613,6370067,6538810,6811067,6887033,6889850,6890712,7359949,13030743,13118565

8221042

Current research on ovine cytokines.

Cytokines are key mediators of the immune system, dictating the quality of the host response to infection. The importance of such immune mediators to the development of immune and inflammatory responses has emerged from work in mouse and man, however it has now become necessary to produce the equivalent (and novel) cytokines in ruminants. Over the past three years recombinant DNA techniques have allowed the cloning of numerous ovine cytokines. These include interleukins -1, -2 and -3 (IL-1, -2 and -3), interferon-gamma (IFN-gamma), ovine trophoblast protein (oTP-1), tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The predicted amino-acid sequences of these ovine proteins show varying degrees of similarity with the equivalent human proteins thus explaining why some of the cytokines are not biologically cross-reactive between species. Recombinant ovine proteins have been produced for IFN-gamma, oTP-1, IL-1, IL-3 and GM-CSF. Their biological activities are very similar to those of their human counterparts. Although it is too early to tell whether the recombinant ovine proteins will be of use in the treatment or prophylaxis of infectious disease, work in cattle and pigs has indicated the potential usefulness of cytokines in this role.

Animals,Cytokines,Immune System,Research,Sheep

1609545,1632079,1652561,1675789,1701245,1709414,1744266,1765267,1769692,1786996,1820971,1836758,1840515,1869289,1902591,1904215,1908159,1919074,1937025,1995858,2105274,2110791,2112286,2115673,2115767,2143038,2204299,2211405,2216781,2251151,2263490,2263496,2405873,2415660,2430188,2446135,2448376,2458335,2460758,2469745,2475963,2497197,2559538,2678728,2686679,2753362,2781045,2784155,2786210,2789243,2797003,2830359,2833332,2834443,2955410,2992320,2997372,3039719,3049913,3052281,3062386,3086437,3093587,3257991,3265477,3356954,3365252,3379349,3431465,3488815,3494788,3495835,3499702,3693903,3871987,6424951,6601146

8221047

The neurotrophic analogue of ACTH(4-9), Org 2766, protects against experimental allergic neuritis.

Demyelinating diseases such as multiple sclerosis or the Guillain-Barré syndrome originate from an autoimmune response resulting in the degradation of myelin and impaired neuronal function. Prophylactic administration of the neurotrophic peptide, H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH [an ACTH(4-9) analogue], to rats with experimental allergic neuritis, a model for the Guillain-Barré syndrome, markedly suppresses the clinical symptoms, protects against loss of motor coordination and prevents the degeneration of myelinated axons in the affected peripheral nerve. Therefore, this peptide may provide a new approach to the therapy of peripheral demyelinating polyneuropathies.

Adrenocorticotropic Hormone,Animals,Female,Locomotion,Movement,Neuritis, Autoimmune, Experimental,Peptide Fragments,Rats,Rats, Inbred Lew,Weight Loss

53392,312920,839247,942051,1334192,1378018,1552913,1552914,1656475,1678980,1682558,1703049,1857491,2067661,2074438,2152972,2166368,2385137,2418761,2440998,2450178,2465636,2536628,2821519,2837394,2838292,2847088,2854241,3260639,3265717,3356993,4622214,5048056,6085109,6124016,6153287,6154892,6304506,6333677,6338293,6389895,6432963,6602381,6974764,7117467,13242745

8221043

Sequence of an exon of the feline p53 gene--mutation in a lymphosarcoma.

Exon 8 of tumour suppressor gene p53 was sequenced in domestic cats and showed remarkable similarity to the human sequence. Only four of the 13 nucleotide differences gave rise to interspecific amino acid differences. In an investigated lymphosarcoma we detected a mutation cgg --> tgg (arginine --> tryptophan) in codon no. 282.

Amino Acid Sequence,Animals,Base Sequence,Cat Diseases,Cats,Codon,Exons,Genes, p53,Humans,Lymphoma, Non-Hodgkin,Molecular Sequence Data,Mutation,Polymerase Chain Reaction,Sequence Homology, Amino Acid

2046748,2142762,2531855,2554494,2649981

8221044

The depletion of glycogen stores and indices of dehydration in transported broilers.

Broilers were either not transported or were transported for 2, 4 or 6 hours after having been subjected to food withdrawal times of less than one hour or of ten hours. The birds were then slaughtered using normal commercial practices. The longer period of food deprivation reduced liver weight and glycogen content, and circulating glucose concentrations. It also elevated the ultimate pH value (pHu) in the biceps muscle and by implication, therefore, reduced its glycogen content. With longer journey times, liver weight and glycogen content decreased. Transport had an inconsistent effect on glycogen concentration in the pectoral muscle but progressively reduced its pHu. In contrast, pHu in the biceps progressively increased, by implication because transport depleted muscle glycogen levels. Birds transported further had higher concentrations of total protein in their plasma which, though this was not significant, also had a higher osmolality. This suggests that transported birds became dehydrated. Additionally, the depletion of body glycogen stores might be associated with the perception of fatigue.

Animals,Chickens,Dehydration,Food Deprivation,Liver Glycogen,Male,Organ Size,Poultry Diseases,Transportation

597736,1275237,2089775,3382974,3918769,6718816,6719773

8221048

Gadolinium enhancement increases the sensitivity of MRI in detecting disease activity in multiple sclerosis.

There is now widespread agreement that serial brain MRI is useful in monitoring treatments designed to modify the course of multiple sclerosis. It has been less clear whether gadolinium enhancement is needed. We therefore compared the relative sensitivity of long repetition time (TR) spin echo (SE) and gadolinium enhanced short TR SE sequences in detecting active lesions. A blind analysis of the two sequences was performed in 26 untreated patients with early relapsing--remitting (19) or secondary progressive (seven) multiple sclerosis who underwent monthly MRI on four occasions (one baseline and three follow-up). Active lesions were defined as either new or enlarged lesions on long TR SE, or new or persistent enhancing lesions on short TR SE. In one patient there were 144 active lesions, all of which were seen with enhancement on short TR SE, but only 17 were seen on long TR SE. Amongst the remaining 25 cases, a total of 106 active lesions were seen: 68 (64%) were seen only with enhancement on short TR SE, 16 (15%) were seen only on long TR SE, while 22 (21%) were active on both sequences. We conclude that gadolinium enhancement markedly increases the sensitivity of monthly brain MRI in monitoring the treatment of relapsing--remitting or secondary progressive multiple sclerosis. With this frequency of scanning, a post contrast short TR SE sequence is the most sensitive method for detecting active lesions. The smaller yet still substantial incidence of active lesions seen only on the long TR SE sequence suggests that it should also be obtained.

Adult,Cerebral Cortex,Gadolinium,Humans,Magnetic Resonance Imaging,Middle Aged,Multiple Sclerosis,Radiographic Image Enhancement,Radionuclide Imaging

1414773,1414831,1431970,1449244,1471866,1497493,1536628,1619410,1636547,1732968,1734325,1782525,1812350,1859184,1866009,1891079,1940938,1996879,2068314,2245307,2300240,2320230,2328409,2505542,2774512,2779420,2913928,3386847,3401689,3419593,3420246,3427402,3488563,3786722,6118521,6847134

8221049

Ocular torsion and perceived vertical in oculomotor, trochlear and abducens nerve palsies.

Ocular torsion (OT) and subjective visual vertical (SVV) were determined in acute and chronic oculomotor (n = 6), trochlear (n = 21) and abducens (n = 7) palsies separately for each eye in the primary position with the head upright. Ocular torsion measured by fundus photographs was not only within normal range in all abducens palsies, but unexpectedly also in 68% of third and fourth nerve palsies which involve oblique eye muscles. Pathological OT, when measurable, was slight (2 degrees - 8 degrees), monocular and occurred either in the paretic or in the nonparetic eye. Subjective visual vertical tilts were more frequent (67% of third and fourth nerve palsies) although mostly small in amplitude (1 degree - 6 degrees). They were confined either to the paretic or the nonparetic eye depending on the duration of the palsy. Determinations of SVV were always normal under binocular viewing conditions. The dissociated occurrence of OT and SVV tilts in the paretic or the nonparetic eye was dependent on the acuteness of the palsy and reflected sensory and/or motor compensation mechanisms. Third and fourth nerve palsies cause only minor and unpredictable monocular OT and SVV tilts as distinct from the frequent binocular and conjugate tilts seen in patients with acute unilateral brainstem lesions.

Abducens Nerve,Adolescent,Adult,Aged,Biomechanical Phenomena,Cranial Nerve Diseases,Eye Movements,Female,Fixation, Ocular,Humans,Male,Middle Aged,Ophthalmoplegia,Paralysis,Torsion Abnormality,Trochlear Nerve

312031,595398,1080373,1080635,4451089,5318285,6881246,7065084,7070775,8498813

8221050

Abnormal spatial localization with trigeminal-oculomotor synkinesis. Evidence for a proprioceptive effect.

We examined spatial localization, using open-loop pointing to visual targets, in a patient with a congenital trigeminal-oculomotor synkinesis. This patient demonstrated abnormal co-activation of the left medial rectus muscle when the left lateral pterygoid contracted. Because one eye could be deviated in the absence of a normal oculomotor innervational command, the efference copy (derived from monitoring of central oculomotor commands) could be dissociated from the proprioceptive afferent signal (determined by the mechanical state of the extraocular muscles). Under conditions of monocular viewing with the normal right eye, when the covered left eye was adducted by the aberrant trigeminal innervation, the patient pointed to the left of the actual position of the target. This finding indicates that proprioceptive afference from the adducted, covered left eye was used in the process of spatial localization. While synkinetic adduction produced a shift in pointing in the opposite direction of rotation of the non-viewing eye, previous studies using passive deviation of the non-viewing eye in normal subjects reported a shift in pointing in the same direction as eye rotation (Gauthier et al., 1990; Bridgeman and Stark, 1991). We propose that this discrepancy is due to the different effects of passive eye rotation and active muscle contraction on the tendon organs of the extraocular muscles. On this basis, we hypothesize that the tendon organs, rather than the muscle spindles, are primarily responsible for the transduction of proprioceptive information about eye position in the orbit.

Adolescent,Eye,Eye Movements,Female,Humans,Jaw,Movement,Muscles,Neural Pathways,Oculomotor Muscles,Proprioception,Tendons,Trigeminal Nerve

104011,107283,553150,1771774,1893990,2141850,2276048,2345630,2630535,2980215,3048612,3488730,3709714,3768184,6214420,6522914,6706509,7268444,7447776,13293270,13909769,14832776,16994401

8221051

Study of selective reaching and grasping in a patient with unilateral parietal lesion. Dissociated effects of residual spatial neglect.

In the present study we investigated the possibility of a dissociation between the visual control of reaching and the visual control of grasping in a prehension task. To this purpose we studied the kinematics of prehension movements in a patient with a right parietal lesion and in six right-handed healthy control subjects. The task we used was one in which the subjects had to reach and grasp target objects in the presence or absence of a simultaneously presented distractor object. All stimuli were presented in the space ipsilateral to the lesion. The distractor could be either of the same or different size to the target object and was presented either to the right or to the left of the target. The following parameters of the prehension 'transport' component were analysed: wrist trajectory, transport time, tangential peak velocity, acceleration. Maximal finger aperture, time to maximal finger aperture, peak acceleration and time to peak acceleration of grip aperture were the parameters of the 'grasping' component analysed. The results showed that, although the patient had no misreaching, her hand trajectory deviated abnormally towards the distractor position when the distractor was to the right (ipsilateral) side of the target. In contrast, the grasp kinematics was not affected by the distractors, even when the size of the right distractor was different from the target. It appears, therefore, that the attentional shift towards the ipsilesional side, typical of neglect patients, determines a surprising dissociation in motor control. In the presence of a right distractor, the patient plans and partially executes a reaching movement towards that object and simultaneously performs a grasping movement towards a second object, i.e. the centrally located target. The presentation of distractors had no effects on the prehension kinematics of the control subjects.

Attention,Biomechanical Phenomena,Brain Diseases,Female,Hand,Humans,Male,Middle Aged,Movement,Parietal Lobe,Psychomotor Performance,Reaction Time,Space Perception,Spatial Behavior

1436435,1571102,1886680,2014049,2124720,2249435,2277540,2302532,2377286,2592524,2758849,3100983,3340293,3502905,3730807,3905583,5061835,6125970,6571312,6640275,6661279,7198201,15151851

8221052

Disturbed frontal regulation of attention in Parkinson's disease.

Parkinson's disease is characterized not only by tremor, akinesia and rigidity, but also by frontal cognitive dysfunction, that can be understood as a disturbance in the 'Supervisory Attentional System' (SAS). This concept refers to a system, located in the frontal cortex, that regulates attentional processes under novel, non-routine conditions. The hypothesis that cognitive dysfunction in Parkinson's disease results from a disturbance in the SAS was investigated by recording 'processing negativity' in 33 parkinsonian patients and 17 controls. Processing negativity is an event-related potential that reflects neuronal activity during selective attention. The contribution of the frontal cortex to selective attention can be studied directly using processing negativity. Parkinsonian patients were also scored for clinical symptoms and subjected to a neuropsychological test battery. Processing negativity was clearly disturbed in the parkinsonian patients. Moreover, parkinsonian patients with the lowest scores on 'frontal' neuropsychological tests such as Stroop, Trail Making and Word Fluency, also had the lowest processing negativity. Our results support the hypothesis that cognitive dysfunction in Parkinson's disease might be understood as a disturbance in the frontal regulation of attentional processes. Degeneration of the dopaminergic mesocortical innervation of the frontal cortex in Parkinson's disease is a possible neurochemical substrate of these frontal attentional disturbances.

Aged,Attention,Brain Diseases,Evoked Potentials,Frontal Lobe,Humans,Middle Aged,Parkinson Disease,Reaction Time

554525,685709,998167,1171402,1688671,1689644,1716570,1895125,2063079,2339190,2444425,2450735,2455629,2471618,2749097,2804609,2923675,2926416,2926417,2927680,2969762,3061477,3193964,3221216,3378138,3378139,3567267,3607146,3705923,3748383,3779372,3779376,3801854,3827218,3945393,3954623,3983301,3995282,4009189,4022359,4730062,6109265,6125971,6158404,6172256,6190637,6198170,6206831,6626985,6736974,6823555,6850270,7114809,7156260,7175557,7202156,7288462,7375620

8221053

Contrasting mechanisms of impaired attentional set-shifting in patients with frontal lobe damage or Parkinson's disease.

Tests which assess the ability to shift cognitive set modelled after the Wisconsin Card Sorting Test are particularly sensitive to impairments in patients with Parkinson's disease as well as in patients with frontal lobe damage. However, the underlying mechanisms responsible for the similar deficits observed in the two patient groups are not well understood and may not be identical. For example, an apparent deficit in set-shifting ability may reflect either an impairment in the ability to shift from a perceptual dimension which has previously commanded attention (i.e. 'perseveration'), or in the ability to shift to an alternative perceptual dimension which has previously been irrelevant (i.e. 'learned irrelevance'). In this study, the performance of both medicated and non-medicated patients with Parkinson's disease were compared with a group of neurosurgical patients with localized excisions of the frontal lobes on a novel task designed to assess the relative contribution of 'perseveration' and 'learned irrelevance' to impaired set-shifting ability. Patients with frontal lobe damage were worse than controls in their ability to shift attention from a previously relevant stimulus dimension. Medicated patients with Parkinson's disease were worse at shifting to a previously irrelevant dimension. In contrast to both groups, nonmedicated patients with Parkinson's disease were impaired in both conditions. These results suggest that the gross set-shifting deficits reported in both frontal lobe patients and patients with Parkinson's disease may involve fundamentally different, though related, cognitive processes, and that these may be differentially affected by medication. Specifically, L-dopa therapy may protect Parkinson's disease patients from preservation of attention to a formerly relevant stimulus dimension.

Aged,Attention,Brain Diseases,Discrimination Learning,Female,Frontal Lobe,Functional Laterality,Humans,Male,Middle Aged,Neuropsychological Tests,Parkinson Disease

1009768,1171402,1202204,1407485,1615139,1641123,1762678,1822726,1869921,1933236,2183676,2290494,2314570,2391523,2391524,2467966,2538773,2545827,2615934,2927625,3085570,3145534,3378139,3670611,3748383,3779372,4009189,4624751,6067254,6084826,6509309,6626985,6646403,6736974,6737043,6850270,6877577,7367577,7410659,13984777,14778049,18874598

8221054

Vestibular induced postural responses in Parkinson's disease.

We have tested the hypothesis that dysfunction of the vestibular control of posture is a principal cause of parkinsonian instability by measuring the body sway response induced by galvanic vestibular stimulation (0.5 mA for 2 s) in a group of patients with Parkinson's disease (n = 15). Responses were compared with those obtained from a group of age-matched control subjects (n = 10). Subjects were stimulated (randomized polarity) whilst standing with feet together, eyes closed and maintaining one of five head yaw angles. The motion of the body and the ground reaction forces were measured in three dimensions. There was no significant difference between patients and controls in the speed or direction of the induced body sway response. When the patients were subdivided into two groups according to a clinical assessment of postural deficit, the more disabled group was found to respond with significantly greater body speed than either the control group or the mildly affected patient group. However, the baseline speed of spontaneous body sway was also greater in these patients and it was found that response speed was linearly related to baseline body sway even for the control group. There were no significant differences between any of these groups in the latency to onset, latency to peak or peak amplitude of the initial horizontal ground reaction force response to the stimulus. We conclude that vestibular dysfunction does not explain the postural deficits of patients who are mildly or moderately affected by Parkinson's disease.

Biomechanical Phenomena,Humans,Middle Aged,Movement,Parkinson Disease,Postural Balance,Posture,Vestibular Diseases

172196,761083,1929231,2364268,2720700,3806114,3955332,4303843,4470421,6293651,6603098,6640269,6842198,6842199,6981783,7397484,8335069,8494334

8221055

Striatal [18F]dopa uptake in familial idiopathic dystonia.

It is known that most cases of idiopathic torsion dystonia (ITD) are inherited in an autosomal dominant fashion. Despite clarification of the underlying genetic defect, no consistent structural lesion has been identified in ITD, and it is probable that a biochemical disturbance is the basis of the disorder. To determine whether there is impaired function of the nigro-striatal dopaminergic terminals in ITD we studied 11 subjects with generalized ITD and a positive family history using [18F]dopa and PET scanning. Of these 11 patients, eight had putamen [18F]dopa uptake within the lower half of the normal range, while three had uptake reduced by > 2 SDs below the normal mean. The lowest putamen [18F]dopa influx constants were found in the most disabled patients. As these reductions were mild it is unlikely that abnormalities of the nigro-striatal dopaminergic pathway are the primary determinant of either the nature of the severity of dystonic symptoms. In addition, we studied three presumed carriers of the ITD gene. These subjects all had normal striatal [18F]dopa influx constants suggesting that [18F]dopa PET is unsuitable as a screening tool for ITD.

Adult,Corpus Striatum,Dihydroxyphenylalanine,Dystonia Musculorum Deformans,Female,Fluorine Radioisotopes,Frontal Lobe,Humans,Male,Middle Aged,Radionuclide Imaging

1681782,2123119,2126684,2132742,2183913,2426591,2576373,2817837,3362365,3966004,4005532,4031909,4055928,5345207

8221056

Patterns of central motor reorganization in hemiplegic cerebral palsy.

Central motor reorganization was studied in 33 subjects with hemiplegic cerebral palsy. Corticospinal projections were investigated using focal magnetic stimulation of the motor cortex. Reflex pathways were examined with digital nerve stimulation. Cross-correlation analysis of multi-unit EMG was used to detect activity in branched common stem last order presynaptic inputs to motor neuron pools. The neurophysiological findings were related to the clinical outcome. In 21 of the subjects studied (64%), there was evidence for reorganization of central motor pathways. The clinical and neurophysiological findings revealed two different forms of reorganization. In both forms focal magnetic stimulation demonstrated novel ipsilateral motor pathways from the undamaged motor cortex to the hemiplegic hand. Ipsilateral projections were not demonstrated from the damaged motor cortex. Eleven subjects had intense mirror movements. In these subjects cross-correlation analysis and reflex testing suggested that corticospinal axons had branched abnormally and projected bilaterally to homologous motor neuron pools on both sides of the spinal cord. The remaining 10 subjects did not have intense mirror movements and in these subjects there was no evidence for last order branching of corticospinal axons. It was found that good function of the hemiplegic hand was associated with the presence of EMG responses in that hand following magnetic stimulation of the contralateral motor cortex. When EMG responses were absent, hand function was poor unless the subject had intense mirror movements.

Adolescent,Adult,Cerebral Palsy,Child,Child, Preschool,Electromyography,Female,Functional Laterality,Hand,Hemiplegia,Humans,Magnetics,Male,Motor Cortex,Movement,Muscles,Neural Pathways,Reflex,Skin

99206,568735,633094,825185,991955,1018273,1374346,1464843,1702111,1705219,1718724,1718725,1864480,1886059,1886063,1891104,1915735,2022247,2074456,2213147,2231421,2231422,2231424,2358550,2621613,2715387,2731028,2927714,2984355,2993087,3038586,3041363,3079553,3202641,3351675,3620943,3724803,3779396,3808256,3964411,4041778,5643345,6276824,6875895,7182471,7310595,13206470,21610900

8221057

The human dorsal hippocampal commissure. An anatomically identifiable and functional pathway.

The hippocampal commissural system in the human brain was found to be similar to that of non-human primates. Three normal serially sectioned human brains were studied in coronal and sagittal sections. Morphological criteria that had been validated in experimental studies on the hippocampal commissures in monkeys (Amaral et al., 1984; Demeter et al., 1985; Lamantia and Rakic, 1990) were applied to the study of these human brains. It was found that while a further reduction in the ventral hippocampal commissure has taken place in human phylogeny leading to its near or total disappearance, the dorsal hippocampal commissure is well developed and represents a sizable fibre tract. It crosses the midline under the rostral portion of the splenium and the caudal part of the body of the corpus callosum. Its fibres as they travel between the splenium and the hippocampal formation attach themselves to the fornix and the inferior portion of the forceps major of the corpus callosum. In its morphology the human dorsal hippocampal commissure fully conforms to that reported in experimental tracer studies in the monkey (Amaral et al., 1984; Demeter et al., 1985). Depth electrode EEG recordings of temporal lobe seizures show, in some instances, a pattern of contralateral spread which strongly suggests that it occurred through the dorsal hippocampal commissure. This statement is based on a careful analysis of the different patterns of contralateral spread of seizure discharge in the light of the known anatomical connections of mesial temporal structures through both direct commissural pathways and through possible indirect ones involving subcortical structures or the frontal lobe. For seizure discharges originating in mesial temporal structures of one side with spread to the contralateral hippocampus before any involvement of the contralateral isocortex the dorsal hippocampal commissure is the only likely pathway of contralateral propagation. Alternative routes appear unlikely in the light of the known primate anatomy of the commissural and other connections of the temporal lobe. Thus humans, despite claims to the contrary (Wilson et al., 1987, 1990, 1991), seem to possess a functional dorsal hippocampal commissure. Some patterns of seizure spread observed in this study which seem to utilize the dorsal hippocampal commissure may be relevant for two phenomena that are of clinical interest: (i) pure amnestic seizures (Palmini et al., 1992); (ii) false lateralization of seizure onset in extracranial EEG recordings in the type III of contralateral seizure spread as defined in this study.

Adolescent,Adult,Child,Electroencephalography,Epilepsies, Partial,Epilepsy, Temporal Lobe,Female,Hippocampus,Humans,Male,Middle Aged,Temporal Lobe

49209,49928,104777,114407,422759,624792,690280,972204,1183418,1222745,1375548,1396429,1628200,1711452,1743154,1745354,1745355,1884756,2086614,2286232,2329189,2439287,2439288,2611680,2820778,3512627,3579221,3611417,3653050,3980771,4106844,4715298,6194969,6433485,6715582,6769979,6808031,7125603,13385382,13596467

8221058

Amygdaloid central nucleus lesions and cholinergic blockade attenuate the response of the renal peripheral benzodiazepine receptor to stress.

Previous research has demonstrated that the density of peripheral benzodiazepine receptors (PBR) in rat kidney rapidly drops following exposure to 80 min of stress. The present experiments examined the contribution of the central and autonomic nervous systems in mediating this effect. Ibotenic acid lesions of the amygdaloid central nucleus (ACe), but not the lateral and basolateral amygdala, diminished the magnitude of the reduction in renal PBR binding caused by stress. Pretreating rats with methyl-scopolamine also inhibited the response of the PBR to stress. Adrenergic blockade with nadolol was ineffective. In order to test whether the PBR was under direct or indirect neural control during stress, unilateral renal denervation was performed. The stress-induced reduction in PBR binding persisted in denervated kidneys revealing that any neural control over the PBR that might exist must be indirect. Together the results suggest that the CNS may be involved in regulating the PBR during stress through the activation of intermediate, possibly hormonal, factors. The involvement of the central nervous system in the modulation of the PBR indicates the relevance of the PBR to physiological adaptations to stress.

Acetylcholine,Amygdala,Animals,Denervation,Ibotenic Acid,Kidney,Male,N-Methylscopolamine,Norepinephrine,Parasympatholytics,Parasympathomimetics,Rats,Rats, Sprague-Dawley,Receptors, GABA-A,Scopolamine Derivatives,Stress, Physiological,Sympathomimetics

20632,40808,221289,835710,918669,1322309,1329114,1647307,1649423,1664066,1664068,1664070,1766554,1780039,1847678,1963260,1963342,2122054,2154488,2154668,2536464,2544879,2552477,2555358,2560776,2574864,2843747,2852369,2854842,2889508,2981667,2988981,2994844,2999338,3016760,3023773,3030512,3031675,3034629,6097917,6132001,6289073,6315880,6322039,6322040,6635005,6667063,14907713

8221059

Chloride current observed as calcium-gated tail current in trigeminal root ganglion neurons of the marine catfish, Plotosus.

Isolated trigeminal ganglion (TRG) neurons of Plotosus in primary culture were studied with patch electrodes in a whole-cell recording configuration. When Ca currents were isolated using electrodes filled with CsCl and Ca buffer in Na- and K-free saline, a large tail current was induced. Both Ca and tail currents were blocked by 2 mM Co2+ in the bath. Reversal potential of the tail current was close to the equilibrium potential for Cl-. The reversal potential was altered by substitution of external Cl- with Br- or methanesulphonate- (MSA-). The anion permeability ratios were estimated as PBr/PCl = 1.95 and PMSA/PCl < 0.05. These results suggested that the tail current was the Ca-gated Cl current. In Plotosus neurons, two types of Ca current, high- and low-voltage activated (HVA and LVA), have been described. Both types of Ca currents were able to induce a tail current. Ba currents through both HVA and LVA channels proved to be ineffective. Upon repetitive activation, the tail current progressively increased in the presence of a nearly constant peak Ca current, and showed a more prolonged complex decay phase. When the electrode was filled with 20 mM EGTA, no tail current was induced, not even after repetitive stimulation. Therefore, the tail current seemed to be regulated by local Ca activity in the vicinity of the membrane. The Ca-gated Cl tail current may regulate the membrane excitability of TRG neurons during repetitive firing.

Animals,Barium,Calcium,Catfishes,Cell Membrane,Cells, Cultured,Chloride Channels,Ion Channel Gating,Ion-Selective Electrodes,Neurons,Trigeminal Ganglion

690884,1335823,1693681,1693766,1941099,2411915,2414437,2426420,2432252,2443667,2445979,2449518,2451213,2457169,2460176,2475816,2482325,2483100,2498663,2556494,2726425,3502143,6096530,6313909,6482969,7153904,7683715

8221060

Colocalization of D1 and D2 dopamine receptor mRNAs in striatal neurons.

There is evidence that D1 and D2 dopamine receptor subtypes coexist at the cellular level in the striatum and act synergistically to mediate the effects of dopamine. Other data suggest that these receptor subtypes are largely segregated in different striatal projection pathways. We used in situ hybridization in serial adjacent 4 microns sections to determine the extent of colocalization of D1 and D2 receptor mRNAs in rat striatal neurons. Cellular localization of D1 and D2 receptor mRNA was performed on section pairs that were hybridized with 35S-labeled cDNA or oligonucleotide probes directed against non-homologous regions of D1 and D2 receptor mRNAs. We found that 26-27% of striatal cells containing one receptor subtype also contained the other subtype. Thus, although D1 and D2 receptors are segregated in the majority of striatal neurons, a substantial number of striatal neurons coexpress both dopamine receptor mRNA subtypes. Our findings provide anatomic support for many of the functional interactions that have been described for D1 and D2 receptors.

Animals,Base Sequence,Corpus Striatum,Male,Molecular Sequence Data,Neurons,RNA, Messenger,Rats,Rats, Sprague-Dawley,Receptors, Dopamine D1,Receptors, Dopamine D2

1281547,1332033,1359451,1695404,1762683,1825357,1826366,1973947,1975640,1977083,2138461,2143777,2144334,2147780,2148707,2168520,2168556,2479133,2531847,2880637,2890403,2958517,2971273,2972814,2974511,3553819,6324982,7679238

8221061

Spinal cord motoneurons express p75NGFR and p145trkB mRNA in amyotrophic lateral sclerosis.

In the present study, in situ hybridization was used to examine the expression of nerve growth factor (NGF) receptor (p75NGFR), trk (p140trk) and trkB (p145trkB) mRNA in spinal cord sections from patients with amyotrophic lateral sclerosis (ALS). We report that the expression of p75NGFR and p145trkB mRNA is elevated in alpha motoneurons in ALS sections. However, p140trk mRNA was not expressed in either ALS or control sections.

Adult,Amyotrophic Lateral Sclerosis,Humans,Middle Aged,Motor Neurons,Proto-Oncogene Proteins,RNA, Messenger,Receptor Protein-Tyrosine Kinases,Receptor, trkA,Receptors, Nerve Growth Factor,Spinal Cord

1281520,1324179,1375039,1465146,1465147,1649007,1649702,1653083,1690677,1710174,1850821,2157470,2159382,2160854,2379826,2483324,2555172,2560649,3022937,7180695,12106299,13400219

8221062

A modality-specific somatosensory area within the insula of the rhesus monkey.

Response properties of neurons in the monkey's granular insula (Ig) were examined with somatic, auditory, visual, and gustatory stimuli. Results indicate that a major portion of Ig is a somatic processing area exclusively, with units that have large and often bilateral receptive fields, consistent with the view that this area serves as a higher-order, modality-specific link in the somatosensory-limbic pathway.

Acoustic Stimulation,Animals,Macaca mulatta,Neurons,Photic Stimulation,Physical Stimulation,Somatosensory Cortex,Taste

111155,1527572,3603028,3793980,4621506,4997565,6125978,6470767,6491723,6616220,7174906,7410614,7410615

8221063

Induction of HSP90 alpha heat shock mRNA after transient global ischemia in gerbil hippocampus.

Distribution of heat shock protein (HSP) 90 alpha mRNA induction after 10 min of transient global ischemia was investigated in gerbil hippocampus by in situ hybridization. A small amount of HSP90 alpha mRNA was normally present in hippocampal cells and the mRNA was further induced with a peak at 8 h after ischemia. In hippocampal CA1 cells that are vulnerable to ischemia, HSP90 alpha mRNA was continuously induced by 1 day and finally diminished at 2 days. The temporal profile of HSP90 alpha mRNA induction in hippocampal CA1 cells was similar to that of HSP70 mRNA reported previously, suggesting a cooperative role of HSP90 alpha with other HSPs after ischemia.

Animals,Carotid Artery, Common,Constriction,DNA Probes,Gerbillinae,Heat-Shock Proteins,Hippocampus,In Situ Hybridization,Ischemic Attack, Transient,Male,RNA, Messenger

1291030,1315915,1506443,1551911,1722411,2016286,2037568,2234079,2427013,2674684,2703487,2768277,2843537,2944601,3019832,3534880,3614648,3776478,3955665,6262754,7093691,7110134,8474691

8221064

Microinjections of subpicomolar amounts of NPY(13-36) into the nucleus tractus solitarius of the rat counteract the vasodepressor responses of NPY(1-36) and of a NPY Y1 receptor agonist.

Microinjections of neuropeptide Y (NPY) (1-36) and of the NPY Y1 agonist [Leu31,Pro34]NPY into the caudal dorsomedial part of the nucleus tractus solitarius (Sol) in the anaesthetized rat led to the development of dose-related vasodepressor and bradycardic responses. The threshold dose of the NPY Y2 agonist NPY(13-36) (50 fmol) significantly counteracted the vasodepressor actions of a close to ED50 dose of NPY(1-36) (2.5 pmol) and of the NPY Y1 agonist (5 pmol). These results indicate that NPY Y1 receptor activation in the Sol leads to the development of a vasodepressor response, which can be counteracted by NPY Y2 receptor activation in the Sol. The results support the existence of a Y2/Y1 receptor-receptor interaction in the Sol, via which NPY Y2 receptors may reduce transduction over NPY Y1 receptors.

Animals,Dose-Response Relationship, Drug,Male,Microinjections,Neuropeptide Y,Peptide Fragments,Rats,Rats, Sprague-Dawley,Receptors, Gastrointestinal Hormone,Solitary Nucleus,Vasoconstrictor Agents

686171,1303142,1386917,1646560,1662423,1664944,1676143,1678015,1978995,2153286,2248040,2259468,2337824,2455156,2558898,2829507,2885349,2909302,3010387,3840887,6137937,6154500,8099435,8422905,20493065

8221065

The caudal ventrolateral medulla is a source of tonic sympathoinhibition.

The caudal ventrolateral medulla (CVLM) contains neurons that are essential for the elaboration of the sympathoinhibitory effects of baroreceptor afferent stimulation. To determine if neurons in the CVLM also mediate a tonic inhibition of sympathetic nerve activity (SNA), we examined the effects of lesioning CVLM neurons in baroreceptor-denervated rats. The sustained increases in both arterial pressure (AP; 40 mmHg) and splanchnic SNA (200%) indicate that the discharge of neurons in the CVLM maintains a tonic sympathoinhibition that contributes significantly to the maintenance of normotensive levels of SNA and AP.

Animals,Baroreflex,Blood Pressure,Denervation,Kainic Acid,Male,Medulla Oblongata,Rats,Rats, Sprague-Dawley,Sympathetic Nervous System

1928446,1933331,2274272,2538087,2732095,2764151,2804685,2833123,2881491,3209808,3567646,3840240,6093929,8381615

8221066

Evidence for localization of the transgene product within axon terminals in the dentate gyrus of transgenic mice expressing human phenylethanolamine N-methyltransferase. A light and electron microscopic immunocytochemical study.

The aim of this study was to examine whether protein products of a transgene are localized within axon terminals in transgenic mice. We have previously created transgenic mice containing a chimeric gene composed of the human dopamine beta-hydroxylase gene promoter and the human phenylethanolamine N-methyltransferase (PNMT) cDNA. In the present study, we used an antiserum that detects specifically human PNMT but not mouse PNMT, and examined immunocytochemically the hippocampal formation of the transgenic mice. At a light microscopic level, immunoreactivity of human PNMT was found in fiber plexuses in the outer molecular layer of the dentate gyrus, and in cell bodies of layer 2 of the entorhinal cortex. At an electron microscopic level, in the outer molecular layer of the dentate gyrus, human PNMT immunoreactivity was observed in axon terminals that formed synapses with dendritic spines. The present study provides the evidence for localization of the transgene's protein products in axon terminals, suggesting axonal transport of the products.

Animals,Axons,Hippocampus,Humans,Immunoenzyme Techniques,Mice,Mice, Transgenic,Microscopy,Microscopy, Immunoelectron,Nerve Endings,Nerve Tissue Proteins,Phenylethanolamine N-Methyltransferase

231924,438367,972204,974734,1504834,1542654,1742021,2282492,2463058,2876401,3607490,6945603,8510498,19215438

8221067

Membrane surface ruffling in cells that over-express Alzheimer amyloid beta/A4 C-terminal peptide.

Deposition of beta/A4 amyloid in brain is a defining characteristic of Alzheimer disease (AD); however, the extent to which amyloid deposits may interfere with normal cellular processes is incompletely understood. We examined this issue by means of PC12 cells. After transfection with DNA coding for 97 amino acids of the beta/A4 C-terminal region of the amyloid precursor protein, beta/A4 antigen was visible at the cell membrane. We report that normal unstimulated PC12 cells exhibit ruffling activity at the cell surface when plated on a plastic substrate. Relative to control cells, however, those that over-expressed the beta/A4 C-terminal peptide had significantly higher levels of ruffling activity, suggesting a structural and/or functional membrane modification. Similar cellular alterations, if present, in Alzheimer brain cells, may indicate disturbances in membrane-associated functions, including intercellular communication.

Alzheimer Disease,Amyloid beta-Peptides,Animals,Cell Membrane,Nerve Tissue Proteins,PC12 Cells

206226,1001364,1372044,1493551,1549777,2082651,2457908,2679112,2681192,2870433,3007528,3159021,3201924,3332661,3332664,3886008,5463639,6141171,6162359,6321519,6411121,6571173,8446172

8221068

Suppression of immunorejection against rat fetal dopaminergic neurons in a mouse brain by 15-deoxyspergualin.

In this study, the immunosuppressive effect of 15-deoxyspergualin (DSG) on the survivability of rat embryonic dopaminergic neurons grafted into the lateral ventricle of adult mice was investigated. DSG was administered daily in dose of 5 mg/kg for 2 weeks postgrafting, commencing on the day of transplantation, in the immunosuppressant-treated groups. Animals were then allowed to survive for 2 to 4 weeks after transplantation. Histological analysis revealed that most of transplanted rat fetal neural tissue was destroyed and scavenged in 2 weeks after transplantation in the non-immunosuppressed group. However, a large number of tyrosine hydroxylase (TH)-positive grafted neurons survived and grew postgrafting in the brain of the host administered with DSG even if they suffered from T lymphocyte infiltrations visualized by cytotoxic T cell immunohistochemistry. The results thus indicated that DSG is an potent immunosuppressant in neural transplantation as well as in transplantation of other organs in animals. It seems to be able to block, at least in part, the ability of mature specific cytotoxic T cells to lyse their targets.

Animals,Dopamine,Fetal Tissue Transplantation,Graft Rejection,Guanidines,Immunosuppressive Agents,Male,Mice,Mice, Inbred C3H,Neurons,Rats,Rats, Sprague-Dawley,Transplantation, Heterologous

1674694,1723023,1975765,1984501,1990605,2105529,2368132,2784883,2877463,2904587,3066438,3214733,3247428,3279613,3279614,3293272,3309054,3402564,3553123,3796814,3919057,3930278,3932581,3974948,4030502,6433204,6926749,19868782,21015608

8221069

c-Fos expression by dorsal horn neurons chronically deafferented by peripheral nerve section in response to spared, somatotopically inappropriate nociceptive primary input.

Subcutaneous formalin injection into the hindpaw of rats induces c-Fos expression in neurons in the ipsilateral spinal cord dorsal horn. In laminae I and II of the dorsal horn at the junction of 4th and 5th segments of the lumbar spinal cord, neurons exhibiting c-Fos protein-like immunoreactivity (Fos-LI) are concentrated in the medial 3/4 that correspond to the terminal field of primary neurons innervating the sciatic nerve. Subacute tibial nerve section 24 h before formalin stimulation caused almost complete elimination of neurons with the formalin-induced Fos-LI in the medial 1/2 (tibial territory) of the above sciatic territory of the dorsal horn. Following a longer survival period (chronic tibial nerve section of 21 days standing), neurons with the formalin-induced Fos-LI re-appeared in the tibial territory. In addition, the number of neurons with the formalin-induced Fos-LI increased in the medial part of the peroneal territory (the lateral 1/2 of the sciatic territory). The results indicate that the activation of c-Fos expression in that part of dorsal horn that has been chronically deafferented by the tibial nerve section is taken over by the spared, but somatotopically inappropriate primary nociceptors. Furthermore, dorsal horn neurons outside but near the deafferented tibial nerve's territory exhibit hypersensitivity to c-Fos expression evoked by intact, somatotopically appropriate primary nociceptive input.

Animals,Denervation,Male,Nerve Tissue Proteins,Neurons, Afferent,Pain,Peripheral Nerves,Proto-Oncogene Proteins c-fos,Rats,Rats, Sprague-Dawley,Spinal Cord

570248,1370574,1407557,1679515,1688935,1748733,1901718,2016421,2113539,2215924,2247318,2426600,2503547,3040178,3112583,3491427,3607438,3968229,4827166,6481639,6498515,6505461,6713208,6824934,7262242,7346576,12106455

8221070

Tyrosine kinase inhibitors, herbimycin A and lavendustin A, block formation of long-term potentiation in the dentate gyrus in vivo.

The effects of two specific tyrosine kinase inhibitors on long-term potentiation (LTP) in the dentate gyrus were investigated using anesthetized rats. I.c.v. injection of herbimycin A (1.74 nmol) or lavendustin A (1.31 nmol) before application of tetanic stimulation significantly inhibited the formation of LTP. However, these inhibitors, when administered after tetanic stimulation, did not affect the established LTP. These results suggest that protein tyrosine phosphorylation is involved in formation of LTP at the dentate gyrus in vivo.

Animals,Benzoquinones,Hippocampus,Injections, Intraventricular,Lactams, Macrocyclic,Long-Term Potentiation,Male,Phenols,Protein-Tyrosine Kinases,Quinones,Rats,Rats, Wistar,Rifabutin

468713,1379306,1450942,1656271,1658554,1664922,1850502,1860069,1981255,2158859,2549638,2614420,2679942,2833996

8221071

c-Fos proto-oncogene activity induced by mating in the preoptic area, hypothalamus and amygdala in the female rat: role of afferent input via the pelvic nerve.

In order to identify brain areas which receive afferent genitosensory input important for mating-induced prolactin release, we compared numbers of Fos-immunoreactive (Fos-IR) cells in brains of intact estrous females 1 h after differential mating stimulation. Numbers of Fos-IR cells were approximately 3-fold higher in the preoptic area (POA), medial amygdala (mAMYG) and bed nucleus of the stria terminalis (BNST) when females received intromissions (I) from males than when they received mounts-without-intromission (M) or were taken directly from their home cage. In the ventrolateral portion of the ventromedial nucleus (VL-VMN), the paraventricular nucleus (PVN) of the hypothalamus and the midbrain central tegmental field (CTF) numbers of Fos-IR cells were significantly higher than home cage levels in groups of females exposed to males regardless of type of mating stimulation received. Bilateral transection of the pelvic nerve eliminated the increases in Fos-IR in POA and mAMYG which occurred in sham-transected females in these areas after intromissions from males. These data demonstrate that afferent input via the pelvic nerve activates cell groups within the POA, mAMYG and BNST and suggests that these areas may be involved in initiation of mating-induced prolactin surges.

Afferent Pathways,Amygdala,Animals,Copulation,Estrus,Female,Gene Expression,Genes, fos,Hypothalamus,Male,Neurons,Pelvis,Posture,Preoptic Area,Prolactin,Rats,Secretory Rate,Sexual Behavior, Animal

482408,959351,986293,1098990,1168131,1315265,1350112,1380440,1436377,1436507,1503660,1523261,1690635,1727695,1903243,2106434,2111893,2112267,2136724,2250236,2298152,2504439,2512584,2691387,2727140,3044519,3112583,3131879,3287417,3340269,3442692,3542515,3726531,3761269,4039418,4059397,4565765,4677202,5008123,5011056,5012741,5100656,5538526,5542775,5892200,6132586,6339213,6403333,6537996,6860975,7188747,7190648,7200424,7466382,8047640,8221135,8440518,13040800

8221072

Calcium-destabilizing and neurodegenerative effects of aggregated beta-amyloid peptide are attenuated by basic FGF.

The mechanisms that contribute to neuronal degeneration in Alzheimer's disease (AD) are not understood. Abnormal accumulations of beta-amyloid peptide (beta AP) are thought to be involved in the neurodegenerative process, and recent studies have demonstrated neurotoxic actions of beta APs. We now report that the mechanism of beta AP-mediated neurotoxicity in hippocampal cell culture involves a destabilization of neuronal calcium homeostasis resulting in elevations in intracellular calcium levels ([Ca2+]i) that occur during exposure periods of 6 hr to several days. Both the elevations of [Ca2+]i and neurotoxicity were directly correlated with aggregation of the peptide as assessed by beta AP immunoreactivity and confocal laser scanning microscopy. Exposure of neurons to beta AP resulted in increased sensitivity to the [Ca2+]i-elevating and neurodegenerative effects of excitatory amino acids. Moreover, [Ca2+]i responses to membrane depolarization and calcium ionophore were greatly enhanced in beta AP-treated neurons. Neurons in low cell density cultures were more vulnerable to beta AP toxicity than were neurons in high cell density cultures. Basic fibroblast growth factor (bFGF), but not nerve growth factor (NGF), significantly reduced both the loss of calcium homeostasis and the neuronal damage otherwise caused by beta AP. In AD, beta AP may endanger neurons by destabilizing calcium homeostasis and bFGF may protect neurons by stabilizing intracellular calcium levels. Aggregation of beta AP seems to be a major determinant of its [Ca2+]i-destabilizing and neurotoxic potency.

Amyloid beta-Peptides,Animals,Calcium,Cells, Cultured,Fibroblast Growth Factor 2,Hippocampus,Homeostasis,Nerve Degeneration,Neurons,Neuropeptides,Rats

1313498,1323483,1346802,1383826,1406936,1439760,1461350,1499683,1531538,1608449,1613515,1647256,1661816,1662517,1663746,1670921,1690006,1690014,1691865,1718986,1719427,1723026,1730616,1738847,1742020,1786545,1793819,1847668,1853202,1865106,1873033,1880556,1899691,1941102,1968460,2002499,2111583,2140897,2146882,2174172,2218531,2251934,2289145,2508225,2554168,2572500,2576507,2585052,2648956,2682327,2769254,2881207,2898515,2900137,2908446,3191384,3224261,3306433,3352734,3367161,3367394,3780919,6375662,7678698,7901348,8094963,8380642

8221073

Cardiac baroreflex dynamics during the defence reaction in freely moving rats.

To determine the extent of baroreceptor reflex involvement in the cardiovascular changes observed during electrically induced defence reaction, the mean arterial blood pressure (MBP) and heart rate (HR) of conscious intact or sinoaortic baroreceptor denervated (SAD) rats were continuously recorded from indwelling cannulae during a 1-min period of electrical stimulation of the mesencephalic tectum. Electrical stimulation produced stimulus intensity-dependent behaviours including freezing at lower intensities and flight at higher intensities. The cardiovascular responses in intact rats were dependent on both the intensity and duration of the stimulus. A linear increase in MBP was observed with increasing stimulus intensities. However, while a slight bradycardia was observed during the freezing behaviour, a marked tachycardia occurred during flight. Simultaneous increases of MBP and HR were seen throughout the first 15 s of the flight response, after which the HR rapidly fell to baseline levels, whereas the MBP remained at a hypertensive plateau until the end of the stimulus. The baroreflex HR curve showed a parallel shift to the left during the first half of the freezing period, being fully reset 40 s after that. So, while the baroreflex gain remained unchanged, the reflex set point was lowered during the freezing stage of the defence reaction. The experiments with SAD rats corroborated the above data. The baroreceptor denervation reversed the freezing bradycardia to tachycardia. Moreover, the denervation potentiated the flight tachycardia and prevented its later reset. MBP responses of baroreceptor denervated rats did not differ from the sham-operated group. The sustained hypertension, thus, appears to be mediated by mechanisms other than the mere baroreceptor reflex deactivation. (ABSTRACT TRUNCATED AT 250 WORDS)

Aggression,Animals,Aorta,Baroreflex,Blood Pressure,Denervation,Electric Stimulation,Electrodes,Heart Rate,Male,Movement,Rats,Rats, Wistar

517664,572871,607247,1147026,1986391,2287484,2758166,2854842,3227948,3234506,3277692,3795103,3796822,3955355,3958439,4672659,5038372,5083171,5102196,5260616,5409868,5449080,5530023,5559629,5816147,5846930,6318241,6657764,6769712,6877597,7174883,7193981,13892393,14243890

8221074

Ventral tegmental microinjection of delta 9-tetrahydrocannabinol enhances ventral tegmental somatodendritic dopamine levels but not forebrain dopamine levels: evidence for local neural action by marijuana's psychoactive ingredient.

Basal extracellular levels of dopamine (DA) and its metabolites in both ventral tegmental area (VTA) and nucleus accumbens (Acb) were simultaneously monitored by in vivo brain microdialysis in laboratory rats. Microinjection of 12 micrograms or 24 micrograms delta 9-tetrahydrocannabinol (delta 9-THC), the psychoactive ingredient in marijuana and hashish, into the VTA produced a dose-dependent increase in somatodendritic DA levels in VTA but failed to produce any simultaneous change in extracellular DA in Acb. Direct delta 9-THC perfusion (5 x 10(-5) and 2 x 10(-4) M) into Acb via the microdialysis probes caused a significant increase in extracellular DA levels in Acb. These findings suggest that (1) delta 9-THC has a facilitating effect on somatodendritic DA efflux, and (2) the elevation of Acb DA levels seen in our previous studies with systemic administration of delta 9-THC may result from local actions of delta 9-THC at or near the DA terminal projections in Acb.

3,4-Dihydroxyphenylacetic Acid,Animals,Dendrites,Dopamine,Dronabinol,Homovanillic Acid,Male,Microdialysis,Microinjections,Prosencephalon,Rats,Rats, Inbred Lew,Ventral Tegmental Area

31529,122445,168349,531077,934055,1114313,1806947,1963849,2177204,2648975,2779859,2852376,2855215,3092066,3490691,3935931,6113601,6278139,6405439,6415748,6609751,6879176,7207031,7266941,7391971

8221075

Kainic acid lesions increase reafferentation of the striatum by substantia nigra grafts.

Effects of kainic acid lesions of the striatum on reafferentation of the striatum produced by intraventricular substantia nigra (SN) grafts were investigated. Rats with unilateral 6-hydroxydopamine lesions of the SN received intrastriatal kainic acid lesions or sham lesions, and then received fetal (E16) SN or sciatic nerve grafts in the lateral ventricle. The depth of reafferentation of the striatum by catecholaminergic neurites from SN grafts was significantly increased in rats with kainic acid-induced striatal lesions, as compared to the sham-lesioned controls. No reafferentation was seen in the control animals with sciatic nerve grafts. These data suggest that striatal injury promotes the growth of dopaminergic neurites from SN grafts.

Afferent Pathways,Animals,Cerebral Ventricles,Corpus Striatum,Fetal Tissue Transplantation,Gestational Age,Kainic Acid,Male,Rats,Rats, Sprague-Dawley,Substantia Nigra,Tissue Donors,Transplantation, Heterotopic

571147,667628,1354165,1680743,1698575,1789541,1915733,1933286,1941074,1978792,2005978,2271940,2327290,2412699,2446902,2648946,2651179,2713080,2865279,2897227,2971786,3047322,3076487,3100320,3111328,3132309,3224261,3249247,3346717,3437470,3463983,3746423,3801914,3970698,3995343,4045554,5494536,6164878,6339524,6368220,6370690,6424029,6426250,6631454,6631476,6635666,6652162,6756547,7195310,7417786,7436393,7683050,8101821

8221076

Cardiac and sympathetic effects of middle cerebral artery occlusion in the spontaneously hypertensive rat.

Acute increases in sympathetic activity, plasma catecholamine concentrations and myocardial damage, occur following middle cerebral artery occlusion (MCAO) in Wistar rats. Hypertension is a major risk factor for stroke. The autonomic responses to MCAO in the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were therefore investigated. Arterial pressure (AP), heart rate (HR), renal sympathetic nerve discharge (SND), plasma catecholamines and ECG were measured in 16 SHR and 16 WKY male urethane-anesthetized rats, which were subjected to either MCAO or sham MCAO. Cerebral infarct size did not differ between SHR and WKY rats, as shown by tetrazolium staining. Initial AP was significantly higher in SHR (96 +/- 4 mmHg) than in WKY (70 +/- 1 mmHg; P < 0.05). No significant differences in initial HR or plasma catecholamine levels were observed between SHR and WKY. By 6 hours after MCAO, AP, SND and plasma epinephrine in SHR decreased significantly, while HR showed a significant increase. SND and plasma catecholamines in the WKY showed increases that did not reach significant levels following MCAO. The QT interval of the ECG was significantly prolonged in the WKY MCAO rats, which also had a higher frequency of cardiac myocytolysis than the other groups. Unlike the increases in autonomic variables following MCAO in Wistar rats, SHR exhibit significant decreases in SND and AP, while WKY show slight, but non-significant increases. These differences in the autonomic reaction to MCAO may reflect genetic differences in the response to cerebral ischemia.

Animals,Blood Pressure,Cardiomyopathies,Catecholamines,Cerebral Arteries,Cerebrovascular Disorders,Constriction,Electrocardiography,Heart,Heart Rate,Hypertension,Male,Rats,Rats, Inbred SHR,Rats, Inbred WKY,Sympathetic Nervous System

178466,505497,675750,1155137,1497495,1695300,1888988,1916993,2007654,2085734,2301638,2564259,2819468,2909296,3385206,3556398,3571525,3585350,3715933,3715954,3719356,3966270,4094719,4387955,6282185,6488025,6498494,6506127,7127079,7130477,7137380,7233464,7237260,7328138,7328139,7339011,13594914,13815638,20242366

8221077

Muscarinic modulation of conductances underlying the afterhyperpolarization in neurons of the rat basolateral amygdala.

The excitability level of pyramidal neurons in the basolateral amygdala (BLA) is greatly increased following muscarinic receptor activation, an effect associated with an increased rate of action potential firing and reduction of the afterhyperpolarization (AHP). We impaled BLA pyramidal neurons in slices of rat ventral forebrain with a single microelectrode to examine the currents underlying the AHP and spike frequency accommodation and determine their sensitivities to muscarinic modulation. In voltage-clamp, depolarizing steps were followed by biphasic outward tail currents, consisting of rapidly decaying (IFast) and slowly decaying (ISlow) current components. These corresponded temporally with the medium and slow portions of the AHP, respectively. The reversal potential for the IFast component of the AHP tail current shifted in the depolarizing direction with increases in the extracellular K+ concentration. The amplitude of IFast was reduced during perfusion of 0-Ca2+ medium or by superfusion of TEA (1-5 mM) or carbachol (10-40 microM). It is suggested that IFast was produced by the rapidly decaying Ca(2+)-activated K+ current (IC) and the muscarinic-sensitive M-current (IM). The ISlow tail current component reversed at the estimated values for EK in medium containing either normal or elevated K+ levels. This component was eliminated by perfusion of 0-Ca2+ medium or inclusion of cyclic-AMP in the recording electrode. It was not blocked by TEA (5 mM) or apamin (50-500 nM), but was reduced by carbachol in a dose-dependent manner (IC50 = 0.5 microM). Electrical stimulation of cholinergic afferent pathways to the BLA produced inhibition of ISlow, an effect which was enhanced by eserine and prevented by atropine. Loss of the ISlow component was always accompanied by similar reductions in accommodation and the slow AHP. It was concluded that this tail current component resulted from the slowly decaying Ca(2+)-activated K+ current, IAHP. Thus, the muscarinic inhibition of IAHP contributes to the enhanced excitability exhibited by BLA pyramidal neurons following cholinergic stimulation.

Amygdala,Animals,Calcium,Electric Conductivity,Electric Stimulation,Male,Membrane Potentials,Neurons,Potassium Channels,Rats,Rats, Sprague-Dawley,Receptors, Muscarinic,Synapses

1338469,1522506,2161530,2299387,2426421,2427553,2443678,2445972,2446253,2451985,2581262,2585290,3253439,3351570,3559710,3585479,3587761,3696492,3886715,3944622,6128061,6185547,6199387,6280066,6291715,6612345,6747887,6875931,6965523,7069469

8221078

Response of neurons in the dorsal motor nucleus of the vagus to thyrotropin-releasing hormone.

Autonomic motoneurons in the dorsal motor nucleus of the vagus (DMX) were recorded intracellularly in an in vitro slice preparation of the guinea pig brainstem. Bath-applied thyrotropin releasing hormone (TRH) (1-10 microM) induced a reversible depolarization of neurons that was typically accompanied by an increase in the spontaneous firing of the cells. In some cells, TRH induced rhythmic bursting activity. The TRH-induced depolarization occurred also in the presence of reduced Ca2+ and TTX. The response was dose-dependent over TRH concentrations of 0.1-10 microM. The TRH-induced depolarization was accompanied by an increase in input resistance. The reversal potential of this effect corresponded to that of K+. Our results indicate that TRH increases the excitability of DMX neurons by reducing a resting K+ conductance.

Animals,Brain Stem,Electric Conductivity,Guinea Pigs,In Vitro Techniques,Membrane Potentials,Motor Neurons,Thyrotropin-Releasing Hormone,Vagus Nerve

104026,224461,401949,404705,416368,823441,825379,889594,1249599,1329553,1354998,1376453,1479442,1692188,1753019,1833029,1873029,1899009,1907074,2106102,2108785,2110196,2125519,2126040,2127304,2166257,2174521,2176434,2408278,2408702,2419787,2428429,2497678,2497682,2498419,2500999,2510096,2559109,2569919,2865733,3082657,3087573,3087574,3090523,3092995,3104750,3108458,3148870,3925552,6019131,6134961,6146119,6201247,6247034,6309326,6403670,6410685,6416344,6416609,6776408,6792542,6793945,6879204

8221079

Spontaneous postischemic hyperthermia is not required for severe CA1 ischemic damage in gerbils.

We have recently shown that brain temperature can drop even though rectal and skull readings are maintained near 37 degrees C during global forebrain ischemia in the gerbil. In this study gerbils were subjected to 5 min of ischemia followed by 85 min of extended halothane anesthesia, while rectal and skull temperatures were kept at normal values. This extended anesthesia procedure prevented the development of spontaneous postischemic hyperthermia. However, it occasionally produced mild brain hypothermia both during ischemia and throughout anesthesia. In addition, the degree of brain hypothermia positively correlated with CA1 preservation; with some gerbils showing complete protection. In contrast, animals with normal brain temperature displayed extensive CA1 cell loss. These data suggest that postischemic hyperthermia is not a prerequisite for extensive CA1 loss in gerbils exposed to 5 min of ischemia. Second, rectal and skull recordings are not always reliable indicators of brain temperature, especially during anesthesia.

Animals,Body Temperature,Brain,Female,Gerbillinae,Ischemic Attack, Transient,Necrosis,Pyramidal Tracts,Rectum,Skull,Time Factors

1180003,1513851,1683472,1731424,1828809,2232868,2347885,2347886,2375631,2771174,3693428,7093691,8448671

8221080

The vascular response to nerve crush: relationship to Wallerian degeneration and regeneration.

The response of the endoneurial vasculature in rat sciatic nerve following crush injury was investigated by morphometric analysis of serial nerve transverse sections at the site of injury and in distal segments at 1, 2, 3, 6, and 9 weeks after injury. Quantitative analysis included determination of the number of vessels, vessel radius vessel perimeter, and transfascicular area. The vascular response to crush injury consisted of two phases: an early phase, which peaked at 1 week after crush, consisted of an increase in vessel size but not vessel number. The second phase, which peaked at 6 weeks after crush, consisted of an increase in the number of vessels and in their density. This two-phase response was also evident as a dual peak in the total endoneurial vessel perimeter, a measure of vascular surface area, when this variable was plotted against time. The first phase of the vascular response was temporally related to the recruitment of macrophages and the clearance of degenerating axonal and myelin tissue during the early phase of Wallerian degeneration. The second phase involved an increase in the number of blood vessels and was associated with cellular proliferation, neurite elongation, and myelination during the subsequent period of nerve regeneration.

Animals,Edema,Female,Hindlimb,Hot Temperature,Nerve Crush,Nerve Regeneration,Pain,Rats,Rats, Sprague-Dawley,Sciatic Nerve,Time Factors,Wallerian Degeneration

428484,475350,1694231,1712736,1732892,2308130,2322838,2445427,2452670,2456134,2457330,2614485,2702606,3340425,3719326,3766120,3929995,3971147,4296122,4700610,5971099,6966527,7223363,13563756,15437207

8221081

Evidence for the involvement of excitatory amino acid pathways in the development of precipitated withdrawal from acute and chronic morphine: an in vivo voltammetric study in the rat locus coeruleus.

Previous studies have demonstrated that activation of excitatory amino acid (EAA) pathways projecting to the locus coeruleus may be involved in the increased firing of locus coeruleus (LC) neurons during opioid withdrawal. Using differential normal pulse voltammetry to monitor catechol oxidation current (CA.OC), an index of neuronal activity in the LC, the role of EAA pathways in naloxone precipitated withdrawal after acute and chronic morphine treatment was examined. Acute morphine treatment (10 micrograms i.c.v.) significantly reduced the CA.OC signal in the LC to 54.3 +/- 3.1% of baseline. Naloxone challenge (1 mg/kg i.v.) completely reversed the morphine effect and produced a significant increase in the CA.OC signal above baseline, peak 145.4 +/- 10.1% of baseline. This naloxone-induced rebound response was attenuated by pretreatment with the EAA receptor antagonists gamma-D-glutamylglycine (DGG) (2, 20, 200 micrograms i.c.v.) and (-)-2-amino-7-phosphonoheptanoic acid (D-APH), but not L-APH (25 micrograms i.c.v.). In chronically morphine-treated rats (25 micrograms/h i.c.v., 5 days), naloxone challenge (1 mg/kg i.v.) produced a significant increase in CA.OC signal, peak 466.5 +/- 112.7% of baseline. This naloxone-induced response was attenuated by pretreatment with DGG (200 micrograms i.c.v.) or D-APH (25 micrograms i.c.v.). To the extent that CA.OC reflects locus coeruleus neuronal activity, the present findings further suggest that increases in locus coeruleus activity during naloxone precipitated withdrawal after both acute and chronic morphine treatment are mediated at least in part by activation of EAA pathways.

2-Amino-5-phosphonovalerate,Amino Acids,Animals,Cerebral Ventricles,Dipeptides,Excitatory Amino Acid Antagonists,Infusions, Parenteral,Injections, Intraventricular,Locus Coeruleus,Male,Morphine,Morphine Dependence,Naloxone,Neurons,Potentiometry,Rats,Rats, Sprague-Dawley,Receptors, Glutamate,Stereoisomerism,Substance Withdrawal Syndrome

191143,216919,562464,573692,574160,824026,1168138,1335354,1683899,1974920,2115910,2187076,2448006,2495149,2556507,2558391,2566932,2569689,2598056,2743108,2760839,2766100,2843624,2874808,2876399,2913267,2988695,3031695,3035579,3091764,3193175,3252031,3335995,3340078,3664267,3742210,3775363,4435020,4473790,4937208,5814495,6092898,6258721,6308694,6324646,6616235,6616236,6682230,6684572,6711824,6890614,7265991,7346592,7346593,12106179,13767428,14229500

8221082

Degeneration of vascular muscle cells in cerebral amyloid angiopathy of Alzheimer disease.

In cerebral amyloid angiopathy, the amyloid-beta (A beta) deposits lie primarily in the tunica media suggesting that smooth muscle cells play an important role in A beta deposition. To define this role, we conducted an immunocytochemical study of brain tissue from cases of Alzheimer disease with extensive cerebral amyloid angiopathy and cerebral hemorrhage. Antibodies specific to recombinant beta protein precursor (beta PP) and synthetic peptides homologous to various beta PP sequences from residue 18 to 689 of beta PP695 were used. Antibodies to actin, tropomyosin, alpha-actinin or desmin were used to label muscle cells. Antibodies to A beta sequences intensely recognized the extracellular amyloid deposit. Antibodies raised against beta PP sequences other than the A beta domain recognized smooth muscle cells. beta PP-immunoreactivity was reduced in regions of A beta deposits, since no muscle cells were recognized by cytoskeletal markers or observed ultrastructurally. In order to assess why A beta is deposited in the tunica media, we used biotin-labelled beta PP to determine if beta PP can be locally retained. We found beta PP bound to the tunica media of vessels but not other brain elements. These findings suggest A beta in blood vessels derives from degenerating beta PP-containing smooth muscle cells.

Actinin,Actins,Aged,Aged, 80 and over,Alzheimer Disease,Amyloid beta-Protein Precursor,Cerebral Amyloid Angiopathy,Cerebral Cortex,Desmin,Female,Humans,Male,Microscopy, Immunoelectron,Muscle, Smooth, Vascular,Tropomyosin

46597,65454,537541,759733,1280517,1434542,1579198,1632466,1716044,1763890,1906461,1918088,1922919,2113083,2113597,2117395,2125517,2260630,2386197,2901596,3029338,3348357,3415200,3655840,3681409,3690426,7153785,7252134

8221083

Distribution of phosphatase inhibitor-1-immunoreactive neurons in the suprachiasmatic nucleus of the Syrian hamster.

The protein phosphatase inhibitor-1 (I-1) is phosphorylated by a cyclic AMP-dependent protein kinase, and is itself involved in the regulation of phosphorylation of other proteins. The enzyme has been shown to be present in skeletal muscles and in distinct neuronal systems of the brain. The suprachiasmatic nucleus is essential in generation of circadian rhythms, but the cellular mechanisms by which the oscillator is entrained are not understood. Since cyclic AMP is known to phase shift the rhythm of electrical activity in SCN neurons in vitro, we aimed by an avidin-biotin immunohistochemical technique to localize I-1-containing neurons in the hamster suprachiasmatic nucleus and thereby identify potential target neurons for cyclic AMP effects. Numerous densely stained neurons were observed in the hamster SCN. The I-1-immunoreactive cell bodies were intermingled with non-immunoreactive neurons and occupied mostly the ventral half of the nucleus, but cell bodies were found in all compartments of the nucleus. The I-1-immunoreactive neurons located in the ventral SCN sent dendrite-like processes into the underlying optic chiasm, indicating that they are directly innervated from the retina, the intergeniculate leaflet of the thalamus, and/or the dorsal raphe. A few I-1-immunoreactive neurons were observed immediately outside the borders of the SCN, but their pronounced staining intensity and their similar morphology to those found inside the SCN indicate that they belong to the same type of neurons as found in the SCN. Delicate I-1-immunoreactive nerve fibers possessing boutons were found throughout the SCN. Furthermore, axonal fibers were followed dorsally into the subparaventricular area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals,Carrier Proteins,Cricetinae,Enzyme Inhibitors,Hypothalamus,Immunohistochemistry,Intracellular Signaling Peptides and Proteins,Male,Mesocricetus,Neurons,Proteins,Suprachiasmatic Nucleus

208844,225171,887940,1353788,1613544,1696252,1700802,1711060,1955581,1978319,2049607,2052155,2052493,2073598,2116813,2413388,2439175,2493406,2538580,2549549,2664825,2668017,2754028,2912504,3101010,3191391,3511054,3768669,3961487,6135628,6151147,6158529,6254089,6259170,6259171,6290217,6313131,6319625,6319627,6501303,19215534,21554586

8221084

Increase in inositol tris-, pentakis- and hexakisphosphates by high K+ stimulation in cultured rat cerebellar granule cells.

Effects of high K+ stimulation on inositol polyphosphate accumulations and intracellular free calcium concentration ([Ca2+]i) were investigated in cultured rat cerebellar granule cells. When the [3H]inositol-labelled cells were stimulated with KCl, concentration-dependent accumulations of [3H]Ins(1,4,5)P3, [3H]InsP5 and [3H]InsP6 were observed. Nifedipine (3 microM), a calcium channel antagonist, inhibited the high (KCl, 90 mM) K(+)-induced accumulations of these inositol polyphosphates. In Ca(2+)-depleted and EGTA-containing (0.1 mM) medium, the high K(+)-induced inositol polyphosphate accumulation were completely inhibited. Similar results were also observed in the case of [Ca2+]i. These results suggest that the rise in [Ca2+]i caused by activation of voltage-dependent calcium channels plays an important roles in the high K(+)-induced accumulation of [3H]Ins(1,4,5)P3, [3H]InsP5 and [3H]InsP6 in cultured rat cerebellar granule cells.

Animals,Calcium,Cells, Cultured,Cerebellum,Inositol 1,4,5-Trisphosphate,Inositol Phosphates,Kinetics,Neurons,Nifedipine,Phytic Acid,Potassium,Rats,Rats, Wistar,Time Factors

1573394,2120216,2226635,2299353,2311765,2338945,2412857,2414684,2547768,2550825,2641883,2722840,2769253,2783453,2784680,2829850,2859852,2884101,2900002,2992357,3016212,3029333,3426614,3499352,3663107,3683585,3838314,3937886,6095092,6095818,6130529,6318733

8221085

The effects of 6-hydroxydopamine lesions of the nucleus accumbens and the mesolimbic dopamine system on oral self-administration of ethanol in the rat.

Rats readily learn to self-administer ethanol using a procedure where ethanol is introduced in the presence of a sweetener. After gradual removal of the sweetener, sufficient quantities of ethanol are self-administered in non fluid-, non food-deprived rats to produce reliable blood ethanol concentrations. Previous studies using this self-administration model have shown that dopamine receptor antagonists injected systemically or directly into the terminal regions of the mesolimbic dopamine system decrease lever pressing for ethanol, suggesting an important role for dopamine in ethanol reinforcement. The purpose of the present study was to test the hypothesis that the mesolimbic dopamine system is a critical substrate for ethanol reinforcement. Results of this study show that 6-hydroxydopamine (6-OHDA)-induced lesions of the mesolimbic dopamine system, sufficient to produce a 93% depletion of dopamine in the nucleus accumbens, an 85% depletion in the olfactory tubercle, an 82% depletion in the frontal cortex and a 78% depletion in the amygdala, failed to alter ethanol self-administration as measured by the total lever presses. However, the 6-OHDA lesion rats showed an altered pattern of responding for ethanol: an increase in the slope of the regression line of cumulative responses vs. time and an increase in the frequency of responding at inter-response intervals of 4-6 and 6-8 s post 6-OHDA lesion; suggesting that this lesion produced a subtle change in motor or attentional function. The results of this study indicate that while the mesolimbic dopamine system may contribute to the reinforcing actions of ethanol, it is not critical for maintaining ethanol reinforcement.

Administration, Oral,Alcohol Drinking,Amygdala,Analysis of Variance,Animals,Body Weight,Corpus Striatum,Dopamine,Frontal Lobe,Limbic System,Male,Motor Activity,Nucleus Accumbens,Olfactory Bulb,Oxidopamine,Rats,Rats, Wistar,Reference Values,Self Administration

38973,282297,354753,531077,551126,1171714,1321582,1365677,1370758,1388276,1561716,1632585,1797032,1968278,2054625,2171372,2222848,2349359,2915601,3080760,3110381,3362929,3530023,3606808,3761194,4332693,6101509,6430466,6438676,6789349,7110328,7183320,7379917,8093596,8095143,8383923,19605016

8221086

Characterization of type A and type B CCK receptor binding sites in rat vagus nerve.

We employed quantitative receptor autoradiography to analyze pharmacological properties of 125I-Bolton Hunter cholecystokinin (CCK-8)-labeled binding sites in sections of rat cervical vagus nerve that had been ligated 24 h prior to extraction. Binding densities were detected in segments of nerve proximal and distal to the ligature. Analysis was confined to proximal segments. Saturation and competitive binding studies were carried out using sulphated CCK-8 and two selective CCK receptor antagonists: MK-329, to define type-A (CCKA) binding sites; and, L-365,260, to define type-B (CCKB) binding sites. Sulphated CCK-8 was the most potent inhibitor of vagal 125I-CCK binding (IC50 = 2 nM). Nonlinear curve fitting analysis of the CCK binding data favored the presence of a single class of vagal CCK receptors (KDi = 1 nM). However, both MK-329 (IC50 = 18 nM) and L-365,260 (IC50 = 45 nM) competed for vagal 125I-CCK binding indicating the presence of CCKA and CCKB binding sites. Co-analysis of the antagonist binding data suggested that CCKA and CCKB receptors were transported in equal concentrations within the vagus. MK-329 bound with high affinity to CCKA sites (Ki = 3 nM) and low-affinity to CCKB sites (Ki = 462 nM) while L-365,260 bound with high affinity to CCKB sites (Ki = 10 nM) and low-affinity to CCKA sites (Ki = 775 nM). These same ligands were used to characterize the specificity of 125I-CCK binding in the medial and lateral divisions of the nucleus of the solitary tract (NTS), two regions innervated by primary vagal afferents carrying CCK receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals,Autoradiography,Benzodiazepinones,Binding Sites,Binding, Competitive,Cholecystokinin,Devazepide,Iodine Radioisotopes,Kinetics,Male,Phenylurea Compounds,Rats,Rats, Sprague-Dawley,Receptors, Cholecystokinin,Sincalide,Solitary Nucleus,Succinimides,Vagus Nerve

1374868,1415646,1631182,1733339,2078822,2257485,2301586,2329368,2441809,2724687,3002550,3214705,3625281,4061684,6168883,6254391

8221087

Ephedrine: effects on neuromuscular transmission.

(-)-Ephedrine has been used in the treatment of patients with myasthenia gravis. To investigate the possible effects of ephedrine on neuromuscular transmission, canine intercostal muscle endplates were studied by microelectrode techniques. At concentrations less than 10(-4) M, ephedrine had no effect on neuromuscular transmission. At a concentration of 10(-4) M, ephedrine increased the quantal content of the endplate potential by 21%. The presynaptic store of acetylcholine quanta available for immediate release was unchanged, but the probability of quantal release was increased by 16%. At this concentration, ephedrine decreased the amplitude of the miniature endplate potential by 38%. In the presence of 10(-3) M ephedrine, the miniature endplate potentials and currents became undetectable. The kinetic properties of the acetylcholine receptor channel were studied by analysis of acetylcholine-induced endplate current noise. At 10(-4) M, ephedrine reduced the channel conductance by 43% but had no effect on the open time. At 5 x 10(-4) M, ephedrine reduced the channel conductance by 84% and increased the open time by 23 percent.

Animals,Dogs,Dose-Response Relationship, Drug,Electric Stimulation,Ephedrine,Evoked Potentials,In Vitro Techniques,Membrane Potentials,Motor Endplate,Neostigmine,Neuromuscular Junction,Synaptic Transmission,Tubocurarine

168841,192885,430403,430489,514458,1375990,1847748,3015341,4347296,4543940,5827910,12106305,13175199,13449877

8221088

Species differences in [125I]interleukin-1 binding in brain, endocrine and immune tissues.

There were dramatic species differences in the level of [125I]recombinant human interleukin-1 alpha ([125I]hIL-1 alpha) binding with high levels of binding present in mouse and rabbit tissues, while no specific binding was present in rat and guinea pig tissues. Utilizing [125I]hIL-1 alpha, moderate to high levels of specific binding were observed in EL-4 6.1 cells (representative of Type I IL-1 receptors) and in mouse hippocampus, spleen and testis; however, no specific [125I]hIL-1 alpha binding was present in Raji cells (representative of Type II IL-1 receptors) and in rat tissues. On the other hand, utilizing [125I]hIL-1 beta, high specific IL-1 binding was present in EL-4 6.1 and Raji cells and moderate binding was evident in mouse tissues, whereas specific [125I]hIL-1 beta binding to rat tissues was not detectable. Moreover, no IL-1 binding in rat tissues was observed using [125I]hIL-1 receptor antagonist, [125I]mouse IL-1 beta or the homologous radioligands [125I]rat IL-1 beta or [125I]rat IL-1 receptor antagonist. These data demonstrate that under optimal conditions for labeling Type I or Type II IL-1 receptors, no specific binding is observed in rat tissues suggesting the presence of novel IL-1 receptor(s) in rat tissues.

Animals,Brain,Cell Membrane,Guinea Pigs,Humans,Interleukin-1,Iodine Radioisotopes,Ligands,Male,Mice,Mice, Inbred C57BL,Organ Specificity,Rabbits,Rats,Receptors, Interleukin-1,Recombinant Proteins,Species Specificity,Spleen,Testis,Tumor Cells, Cultured

1386414,1460092,1532025,1647302,1826616,1826879,1828896,1833184,1833666,1838480,1967907,1992828,2141815,2147409,2443979,2521831,2527495,2530579,2530580,2560554,2651094,2676681,2786888,2820704,2821621,2955042,2960676,2972289,3277884,25291552

8221089

Effects of noise stimulation on cochlear dopamine metabolism.

Dopamine (DA) appears to be one of the putative neurotransmitters of the lateral efferent olivocochlear fibers. However, its role in the cochlear physiology remains unknown. In this study, animals were exposed for 1 h to white noise at 70, 90 or 110 dB SPL or were kept in silence conditions. Afterwards, the cochlear content of DA and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were analyzed using HPLC coupled to electrochemical detection. Cochlear DA concentration decreased with the noise intensity, while cochlear DOPAC and HVA concentrations increased. Males presented higher cochlear DOPAC contents and lower HVA contents than females. This sexual dimorphism could be related to the link between DA and gonadal steroids. Present results show that DA, as other lateral efferent neurotransmitters, is released and metabolized in relationship with the noise stimulation, and suggest that DA could be involved in the modulation of the type I afferent fiber activity.

3,4-Dihydroxyphenylacetic Acid,Acoustic Stimulation,Animals,Cochlea,Dopamine,Female,Homovanillic Acid,Male,Rats,Sex Factors

206175,1383428,1487696,1763623,2298391,2752573,2890616,2903609,2951620,3065792,3664268,3915090,5672445,6203722,20492917

8221090

Alpha 1-adrenoceptors in the adult rat barrel field: effects of deafferentation and norepinephrine removal.

Norepinephrine (NE), acting on brain adrenoceptors, plays an important role in barrel field neuronal activity and plasticity. For this reason, the distribution of alpha 1- and alpha 2-adrenoceptors in the somatosensory cortex barrel field was studied by autoradiographic techniques in rats undergoing plastic change or NE depletion. In layers IV and V of the cortex, the pattern of alpha 1-adrenoceptors (assessed by [3H]prazosin binding) varied across the barrel field. There was relatively low binding within the barrels themselves, with 21% higher binding in the surrounding septa. alpha 2-Adrenoceptor binding (assessed with [3H]paraminoclonidine) was almost homogeneous across the entire barrel field. Two weeks after noradrenergic deafferentation by unilateral lesioning of the locus coeruleus, there was a 16% upregulation of [3H]prazosin binding. This then returned to control levels of by 8 weeks. Peripheral deafferentation of sensory input to the barrel field produced the opposite effect on alpha 1-adrenoceptors. Unilateral removal of all but the central (C3) vibrissa (which induces plastic changes in the cortical representation of the spared virbrissa) caused a 12% decrease in [3H]prazosin binding in the whole barrel field at 2 weeks after surgery which returned to normal by 8 weeks. Therefore, alpha 1-adrenoceptors in the barrel field of the rat are affected in opposite ways by changes in NE content and afferent sensory input. We hypothesize that alpha 1-adrenoceptor levels are modulated after vibrissectomy through either an indirect reaction to reduced cortical gamma-aminobutyric acid levels, or by a reordering of metabolic priorities during plastic change of the cortical neuronal network.

Afferent Pathways,Analysis of Variance,Animals,Autoradiography,Functional Laterality,Locus Coeruleus,Male,Neurons,Norepinephrine,Prazosin,Rats,Rats, Sprague-Dawley,Receptors, Adrenergic, alpha-1,Receptors, Adrenergic, alpha-2,Somatosensory Cortex,Time Factors,Tritium,Vibrissae

37512,223866,429612,770516,904693,904694,1531989,1677306,1701263,1769385,1868907,2164222,2298933,2416396,2510906,2551054,2648946,2707320,2821227,2822774,2823969,2841011,2918357,2981906,2987756,3005879,3032371,3121136,3129134,3703001,4904874,6125573,6140996,6175853,6198035,6246540,6258960,6311335,6316208,6512012,7346572,7439284,8479290

8221091

Regional cerebral blood flow changes of cortical motor areas and prefrontal areas in humans related to ipsilateral and contralateral hand movement.

The regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) in ten normal right-handed volunteers with the purpose of comparing rCBF changes related to movements of the dominant (right) and non-dominant (left) hand. The hand movement task consisted of sequential opposition of the thumb to each finger. The rCBF measured was compared with a rest state. Movements of the dominant hand and the non-dominant hand, increased CBF significantly in the contralateral motor area (MA) and the premotor area (PMA) with small increases in rCBF in the supplementary motor area (SMA). However, movements of the non-dominant hand also elicited significant ipsilateral increases in rCBF in the MA and PMA (6.3% and 5.0%, respectively). Superior part of the prefrontal area (PFA) of the left hemisphere showed significant CBF increases to both left and right hand movement. Our findings indicate that rCBF changes in the motor areas and the PFA of one hemisphere are not related simply to movement of the contralateral hand. Non-dominant hand movement may in addition require activation of ipsilateral motor areas. That is, there appears to be functional asymmetry in the MA and PFA in humans even in this relatively simple and symmetric motor task.

Adult,Analysis of Variance,Brain Mapping,Dominance, Cerebral,Functional Laterality,Hand,Humans,Male,Motor Activity,Motor Cortex,Movement,Prefrontal Cortex,Regional Blood Flow,Tomography, Emission-Computed

28540,100584,107282,570672,591992,708500,827962,942309,942312,1252960,1688771,1726605,1875248,2045890,2065746,2271951,2358882,2396097,2676883,2789231,3083499,3262113,3404223,3494107,3558879,3572473,3600757,3622679,3718289,3877309,3994562,4196203,4351192,4436696,4687784,4961643,5013685,5132963,6610024,6673997,6715206,6971299,6981690,7069449,7238911,7248755,7296262,7310431,7351547,7351548,12106169,12106378,12106480,14392225

8221092

Systemic or intracerebroventricular injection of NMDA receptor antagonists attenuates the antinociceptive activity of intrathecally administered NMDA receptor antagonists.

We have previously reported that the response latency in the mouse hot-plate test is affected differently by spinal intrathecal (i.t.) injection of competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, in that only the former produces an antinociceptive effect. Since the lipophilic non-competitive antagonists will redistribute rapidly from the spinal injection site, it is conceivable that they reach sites where they counteract the spinal antinociceptive effect. In the present study, we have tested this hypothesis by comparing the antinociceptive effect of the competitive NMDA receptor antagonist CGS 19755 and the non-competitive NMDA receptor antagonist MK-801 after i.t., intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration as well as after combinations thereof. CGS 19755 injected i.p. or i.c.v. and MK-801 injected i.p. or i.t. attenuated the antinociceptive effect of i.t. injected CGS 19755. Both i.p. and i.c.v. administration of either CGS 19755 or MK-801 dose-dependently impaired motor function without producing antinociceptive effects. Thus, the effect of CGS 19755 and MK-801 on the motor system was found to be separate from their antinociceptive effect. In a separate experiment, changes in hind-paw skin temperature were excluded as a possible confounding factor. These findings demonstrate that supraspinal systems can limit the spinal antinociceptive effect of NMDA receptor antagonists.

Animals,Cerebral Ventricles,Dizocilpine Maleate,Dose-Response Relationship, Drug,Hot Temperature,Injections, Intraperitoneal,Injections, Intraventricular,Injections, Spinal,Mice,Mice, Inbred Strains,N-Methylaspartate,Pain,Pipecolic Acids,Receptors, N-Methyl-D-Aspartate,Skin Temperature,Spinal Cord,Time Factors

496056,1313371,1347242,1347650,1352804,1356265,1535594,1647967,1674413,1676144,1718010,1724310,1814555,1828310,1828877,1831907,1836763,1921412,1975091,1975214,2155495,2162711,2168102,2405111,2425302,2481030,2553203,2553930,2563331,2821443,2822907,2823998,2828564,2841001,2862229,2872283,2890415,2898513,2899170,2906415,2907372,3012402,3380319,3380562,3529096,3742230,4338478,6131834,6143527,6147787,6149792,6317114,6877845,6893963,7058060,8430132

8221093

Intranigral injections of SCH 23390 inhibit amphetamine-induced rotational behavior.

Rats were given unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway and permanent indwelling cannula were surgically implanted into the non-lesioned side of the brain; cannula were used for direct injections of dopamine antagonists into the pars reticulata region of the non-lesioned substantia nigra. The selective D1 receptor antagonist, SCH 23390, was injected intranigrally at various concentrations (3.0, 1.5, 1.0, 0.6, or 0.3 mM) just prior to an intraperitoneal injection of amphetamine. SCH 23390 dose-dependently inhibited amphetamine-induced rotational behavior with the highest doses completely blocking rotational behavior in some animals. An intranigral injection of the selective D2 receptor antagonist, (-)-sulpiride (1.0 mM), did not produce a significant reduction in amphetamine-induced rotational behavior whereas an equivalent molar concentration of SCH 23390 (1.0 mM) produced a significant 62% reduction in amphetamine-induced rotational behavior. A concentration of SCH 23390 that produced a 50% reduction in rotational behavior when injected directly into the substantia nigra was unable to produce a significant reduction in rotational behavior when injected directly into the striatum. The effects of intranigral injections of SCH 23390 on apomorphine-induced rotational behavior were directly opposite to that observed for amphetamine-induced rotational behavior; contralateral rotational behavior increased relative to baseline measures. These data support the hypothesis that dopamine release in the midbrain may act as a neuromodulator of motor behavior, and that D1 receptors play a functional role in this process.

Amphetamine,Analysis of Variance,Animals,Apomorphine,Benzazepines,Corpus Striatum,Dose-Response Relationship, Drug,Male,Microinjections,Motor Activity,Oxidopamine,Rats,Rats, Sprague-Dawley,Rotation,Stereotaxic Techniques,Substantia Nigra,Sulpiride,Time Factors

13499,575196,696468,811329,1111820,1256566,1256567,1712381,2479133,2572004,2795165,2868905,2901690,2949066,2971144,3014800,3159011,5494536,6105003,6148252,6413983,6439567,6525513,6607768,6640328,6828891,7374778,7412875,19604848,19605258,20493000

8221094

Brain blood flow restoration 'rescues' chronically damaged rat CA1 neurons.

Middle aged rats (13 months) were subjected to chronic cerebrovascular insufficiency (CVI) for 9 weeks using a 3-vessel occlusion technique. This CVI injury targets CA1 neuron damage selectively. Three groups of rats had their cerebral blood flow restored after 1, 2 or 3 weeks following CVI by removal of their carotid artery occluders. Another rat group did not undergo deocclusion for the 9 week observation period. Rats were tested for memory acquisition and retention 6 and 9 weeks after CVI using a modified water maze test. At the end of the 9 weeks, cerebral blood flow was measured in the fronto-parietal cortex and rats were killed by fixation-perfusion. Hippocampal morphometry was done to assess the % of damaged CA1 neurons and the density of GFAP-positive hyperplasia and hypertrophy. Results show that restoration of cerebral blood flow 1 and 2 weeks after CVI but not after 3 weeks of CVI, reversed a significant increase in reactive astrocytosis and prevented memory impairment in these deoccluded rats when compared to the non-deoccluded group. It appears from these results that 'neuronal rescue' of CA1 neurons is possible when cerebral blood flow is restored in rats subjected to chronic CVI during a 2 week (but not 3 week) 'window of opportunity'. This chronic brain ischemia model may be useful in screening potential therapy in patients with dementia where spatial memory impairment and hippocampal damage may be manifested.

Analysis of Variance,Animals,Brain,Brain Ischemia,Cell Division,Cerebrovascular Circulation,Glial Fibrillary Acidic Protein,Hypertrophy,Male,Memory,Neurons,Pyramidal Tracts,Rats,Rats, Sprague-Dawley,Regional Blood Flow,Space Perception

506774,561903,848276,1180003,1252685,1327402,1355882,1548296,1561675,1579973,1595393,1663712,1852179,1927257,2013308,2042939,2049602,2054660,2079719,2195717,2250705,2290611,2296379,2572985,2797444,2812317,2856948,2878711,3178529,3194063,3259296,3289686,3541046,3760943,3810715,3860085,6276420,6353837,6475501,6602819,6603596,6707703,7078359,7088155,7093691,7190246

8221095

Intravenous administration of inorganic selenium compounds, inhibitors of prostaglandin D synthase, inhibits sleep in freely moving rats.

Prostaglandin (PG) D2 has been postulated to be an endogenous sleep-promoting factor. Biosynthesis of PGD2 is catalyzed by PGD synthase (prostaglandin-H2 D-isomerase, EC 5.3.99.2), the activity of which is inhibited by inorganic selenium compounds such as SeCl4 and Na2SeO3. We recently examined the effect of intracerebroventricular administration of these selenium compounds on sleep in rats, and demonstrated time- and dose-dependent sleep inhibition. To establish whether this effect of selenium is also produced when the compound is administered systemically, we devised a procedure for intravenous catheterization and examined the effect of these selenocompounds on sleep-wake activity in freely moving rats (n = 35). Each test compound was administered into the inferior vena cava continuously between 11.00 and 17.00 h on the experimental day. SeCl4 time- and dose-dependently inhibited sleep at infusion rates of 5, 7.5, 10 and 20 nmol/microliters per min. During the SeCl4 infusion at 20 nmol/microliters per min, slow-wave sleep and paradoxical sleep were reduced to 63% and 50% of their respective baseline values. Na2SeO3 exhibited a similar sleep inhibition, though Na2SO3 was ineffective. Infusion of SeCl4 at 10 nmol/microliters per min or below produced no consistent changes in the mean brain temperature, or food and water intake during the infusion period. During the nocturnal period subsequent to SeCl4 infusion, sleep was increased by a rebound phenomenon, while a decrease in brain temperature and inhibition of food and water intake dose-dependently occurred. We conclude that systemic administration of these PGD synthase inhibitors has a sleep-reducing potency.

Animals,Chlorides,Electroencephalography,Electromyography,Infusions, Intravenous,Intramolecular Oxidoreductases,Isomerases,Lipocalins,Male,Rats,Rats, Sprague-Dawley,Selenium Compounds,Sleep,Sodium Selenite,Time Factors,Wakefulness

986515,1100437,1711888,1858872,1907936,1910313,1924366,2105164,2142875,2720378,2730591,2795237,2804673,2841842,3049580,3163802,3300734,3390461,3922798,3996611,4040194,4416312,4686466,4757382,4828478,5283470,5364291,5499302,5690010,6172286,6572936,6766657,6829749,7219462,7377334,7406957,11515060,24272892

8221096

Sensory responsiveness of brain noradrenergic neurons is modulated by endogenous brain serotonin.

Previous results have indicated that application of serotonin (5-HT) onto noradrenergic locus coeruleus (LC) neurons selectively attenuates the response of these cells to excitatory amino acids (EAAs). Other studies revealed that certain sensory responses of LC neurons are mediated by EAA inputs. We examined the role of endogenous 5-HT in modulating sensory responses of LC neurons that are EAA-mediated. LC neurons recorded in rats pretreated with the serotonin (5-HT) depletor, p-chlorophenylalanine (PCPA), exhibited increased responsiveness to electrical stimulation of a rear footpad. Conversely, injection of the 5-HT precursor, 5-hydroxytryptophan (5-HTP), reversed this effect of PCPA and attenuated this sensory response of LC neurons in drug-naive animals. Neither treatment altered the spontaneous discharge rate of LC neurons. These results are consistent with previous findings indicating that 5-HT has potent but selective effects on EAA-mediated responses of LC neurons, and in addition point to a possible functional role for endogenous 5-HT in controlling sensory-evoked LC activity.

5-Hydroxytryptophan,Animals,Brain,Electric Stimulation,Evoked Potentials,Fenclonine,Hindlimb,Male,Neurons,Neurons, Afferent,Rats,Rats, Sprague-Dawley,Sciatic Nerve,Serotonin

19125,154620,156574,439032,1346944,1672153,1905186,2017456,2338658,2526217,2576315,2847343,2867807,2893990,2897873,2897880,3061564,3096493,3193175,3275471,3719350,5297133,5566671,6103735,6124300,6134247,6138137,6193764,7346593,7421993,8101639,20493020

8221097

Neuron-specific enolase increases in cerebral and systemic circulation following focal ischemia.

Neuron-specific enolase (NSE) is an isoform of the glycolytic enzyme, enolase, and is found in neurons and neuroendocrine cells. We evaluated cerebral immunohistologic and plasma changes in NSE in rats from 2 h to 15 days following permanent or transient middle cerebral artery occlusion (MCAO). At 1-2 days post-MCAO, loss of NSE immunofluorescence from within neurons to the extracellular space was observed in the infarcted areas of all MCAO animals. NSE also was identified intravascularly throughout the brain following MCAO. NSE in plasma was determined by a specific radioimmunoassay. Plasma NSE following permanent or transient MCAO was increased significantly from that observed in controls (2.8 +/- 0.3 ng/ml) beginning at 2 h and persisting for 2.5 days post-MCAO (maximum levels of 8.8 +/- 0.9 to 9.6 +/- 0.5 ng/ml after 6-12 h; P < 0.05, n = 4-9). Quantified contralateral forelimb and hindlimb neurological deficits in these animals were significant and persisted for at least 15 days following MCAO but were not observed following sham surgery. These data suggest that MCAO-induced cortical infarction and neurological dysfunction is associated with neuronal depletion and vascular redistribution of brain NSE resulting in a measurable increase in plasma NSE. Such diffusion of NSE into the cerebral vasculature and systemic circulation from ischemic tissue can be expected to serve as a marker for the incidence of cerebral damage in acute and chronic ischemic brain infarcts.

Animals,Biomarkers,Brain Ischemia,Cerebral Arteries,Forelimb,Frontal Lobe,Functional Laterality,Ischemic Attack, Transient,Male,Motor Activity,Neurons,Phosphopyruvate Hydratase,Rats,Rats, Inbred SHR,Time Factors

110910,1381529,1458320,1605077,1606499,1630732,1656059,1752289,1876966,1940312,2742544,2809727,3413812,3551759,3629651,3715945,6317805,6355398,6356007,6726246,6747647,6782195,7045288,7135210,7334408,7373305,8495380,20487894,20487935

8221098

Generation of a monoclonal antibody specific for a new class of minor ganglioside antigens, GQ1b alpha and GT1a alpha: its binding to dorsal and lateral horn of human thoracic cord.

We have established a monoclonal antibody, GGR41, specific for a new class of minor gangliosides, such as GQ1b alpha and GT1a alpha, by immunizing mice with a GQ1b-rich ganglioside fraction extracted from bovine brain. Each of those minor gangliosides has been reported to be one of the cholinergic-specific gangliosides (Chol-1). Careful examination of binding specificity of the antibody by both an enzyme-linked immunosorbent assay and immunostaining on thin-layer chromatograms showed that the antibody recognizes three sialyl residues separately attaching to the gangliotetraosyl backbone structure. Immunohistochemical analysis revealed that GGR41 immunostained lamina I and III of dorsal horn and lateral horn of human thoracic cord but motor neurons were not immunostained. Except for negative staining of motor neurons, this distribution is similar to the distribution pattern of staining as reported in rats and humans using a polyclonal antibody against Chol-1. Thus, the antibody obtained in this study should be a useful reagent to study the function of a unique new class of the minor gangliosides.

Animals,Antibodies, Monoclonal,Antigen-Antibody Complex,Carbohydrate Conformation,Carbohydrate Sequence,Chromatography, Thin Layer,Enzyme-Linked Immunosorbent Assay,Gangliosides,Humans,Immunohistochemistry,Mice,Mice, Inbred C3H,Molecular Sequence Data,Spinal Cord

1515593,1587788,1618794,1627599,1922925,2353821,2776024,3169197,3757018,6193515,6207435,7020949,7023369,7042914,20487978

8221099

Growth hormone release evoked by electrical stimulation of the arcuate nucleus in anesthetized male rats.

Plasma growth hormone (GH) concentrations were measured following electrical stimulation of either the arcuate nucleus or the median eminence in urethane-anesthetized male rats. While electrical stimulation of the arcuate nucleus elicited a large pulse of GH secretion, stimulation of the median eminence was relatively ineffective. For stimulation of the arcuate nucleus, the frequency dependence of stimulus-secretion coupling for GH release was investigated by delivering 3 differing patterns of electrical stimulation, each of 2 min duration and containing 1,200 stimulus pulses: 10 Hz continuous; 20 Hz (10 s on/10 s off); and 50 Hz (2 s on/8 s off). To examine the effect of increasing the duration of the 50 Hz stimulus train on evoked GH release, a further three stimulation protocols were also tested: 50 Hz (2 s on/8 s off); 50 Hz (3 s on/7 s off) and 50 Hz (4 s on/6 s off). While evoked GH release (per stimulus pulse) was not significantly different for various frequencies of stimulation, it was greatly potentiated by increasing the duration of 50 Hz stimulus trains. These findings suggest that GH release is not linearly related to the activation of GRF neurons but is strongly facilitated with increases in burst duration.

Animals,Arcuate Nucleus of Hypothalamus,Electric Stimulation,Growth Hormone,Growth Hormone-Releasing Hormone,Luteinizing Hormone,Male,Median Eminence,Rats,Rats, Wistar,Time Factors

35340,203009,874400,1608512,2423991,2432203,2465137,2850339,2862007,2864380,2869425,3085867,3108692,3783083,4577217,5025691,5027166,6124897,6128220,6131728,6149116,6652482,6716296,7252399,7432096

8221100

Transitional properties of the mechanically evoked perioral reflex from infancy through adulthood.

The organization of motor responses in the orbicularis oris muscle following the delivery of punctate mechanical inputs to vermilion skin of the lips was studied in a group of young infants, school-age children, and adults during periods of voluntary lip muscle activation. A specially designed multi-point array skin contactor, coupled to a position-servo controlled linear motor, was highly effective in driving the early component of the perioral reflex (R1). Overall, the evoked R1 response obtained from the infant was of variable amplitude relative to the children and adults, lacked response specificity, and occurred at a longer latency. This brainstem mediated sensorimotor action appears to take on several characteristics of the adult form by the age of 12. The emergence and maturation of mechanically evoked perioral reflexes is discussed in relation to the acquisition of motor skills, including speech and smiling.

Adolescent,Adult,Aging,Child,Child Development,Child, Preschool,Electromyography,Humans,Infant,Lip,Models, Neurological,Muscles,Physical Stimulation,Reaction Time,Reflex

148310,703277,1493544,1708714,1842699,2213312,2611649,2993086,3224424,3560900,3569454,3666076,4031995,6057506,6169502,6875895,7172010,12978170,14402999,14910816,15140689

8221101

Differential effects of specific delta and kappa opioid receptor antagonists on the bidirectional dose-dependent effect of systemic naloxone in arthritic rats, an experimental model of persistent pain.

In an attempt to determine the opioid receptor class(es) which underly the two opposing effects of naloxone in models of persistent pain, we tested the action of the selective delta antagonist naltrindole, and that of the kappa antagonist MR-2266 on the bidirectional effect of systemic naloxone in arthritic rats. As a nociceptive test, we used the measure of the vocalization thresholds to paw pressure. The antagonists were administered at a dose (1 mg/kg i.v. naltrindole, 0.2 mg/kg i.v. MR-2266), without action per se but which prevents the analgesic effect of the delta agonist DTLET (3 mg/kg, i.v.) or the kappa agonist U-69,593 (1.5 mg/kg, i.v.) respectively, and does not influence the effect of morphine (1 mg/kg i.v.) or the mu agonist DAMGO (2 mg/kg, i.v.) in these animals. In arthritic rats injected with the delta antagonist, the paradoxical antinociceptive effect produced by 3 micrograms/kg i.v. naloxone was not significantly modified (maximal vocalization thresholds (% of control) were 146 +/- 9% versus 161 +/- 7% in the control group). By contrast, the hyperalgesic effect produced by 1 mg/kg i.v. naloxone was significantly reduced (maximal vocalization thresholds were 87 +/- 4% versus 69 +/- 5% in the control group). In rats injected with the kappa antagonist, the antinociceptive effect of the low dose of naloxone was almost abolished (mean vocalization thresholds were 115 +/- 3% versus 169 +/- 7%) whereas the hyperalgesic effect of naloxone 1 mg/kg i.v. was not significantly modified (mean vocalization thresholds = 70 +/- 3% and 65 +/- 3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance,Animals,Arthritis,Benzomorphans,Dose-Response Relationship, Drug,Injections, Intravenous,Male,Naloxone,Naltrexone,Narcotic Antagonists,Nociceptors,Pain,Pain Threshold,Rats,Rats, Sprague-Dawley,Receptors, Opioid, delta,Receptors, Opioid, kappa,Vocalization, Animal

131876,1317026,1317544,1319338,1335878,1382800,1594104,1651143,1653636,1654538,1655159,1664330,1666049,1684729,1817726,2173962,2436100,2540325,2549383,2559347,2566136,2571723,2776018,2790459,2825045,2829060,2838307,2900057,2906425,3011202,3025002,3032345,3040975,3217532,3547255,3580112,3714107,6086366,6247014,6424884,6574799,7454381,8392893

8221102

Glycogen in astrocytes: possible function as lactate supply for neighboring cells.

In order to contribute to the elucidation of the function of astrocyte glycogen in brain, studies on the fate of the glucosyl residues of glycogen were carried out on astroglia-rich primary cultures derived from the brains of newborn rats. On glucose deprivation astroglial cells rapidly deplete their glycogen. In contrast to the situation with hepatocytes, only lactate, but not glucose, is detectable in the medium surrounding the astroglial cells. Besides glucose, astroglial cultures can also use mannose as a substrate for the synthesis of glycogen and the generation of lactate. Although mannose-fed astroglial cells contain glucose-6-phosphate, they do not release a measurable amount of glucose into the culture medium. Instead of glucose the astroglial cells release high amounts of lactate into the culture medium. Gluconolactone or 2-deoxyglucose which prevent glycogen breakdown in astroglial cells after glucose deprivation, allow to discriminate between lactate generated from glycogen and lactate from other sources. The amount of lactate found in the medium in the absence of gluconolactone (or 2-deoxyglucose) exceeds the amount found in the presence of either compound by the lactate equivalents calculated to be contained in the cellular glycogen. In conclusion, glycogen in astrocytes can be considered as a store for lactate rather than for glucose.

Animals,Astrocytes,Cells, Cultured,Glucose,Glycogen,Lactates,Liver

27582,169241,182319,1691273,1729397,1815828,1850300,1919582,1967630,2027525,2085749,2163018,2282504,2351562,2523335,2835334,2900788,2903222,2976396,2985921,2990038,3001224,3018195,3052289,3183664,3186756,3378257,3380321,3385482,3503501,3503929,3552790,3964824,4198154,5944237,6118864,6123954,6140646,6156399,6220021,6801208,6834050,6991644,7005399,7005401,7007577,8225556,8455036,11946971,13211595,14907713

8221103

Chlordiazepoxide attenuates stress-induced accumulation of corticotropin-releasing factor mRNA in the paraventricular nucleus.

Corticotropin-releasing factor (CRF) plays a role in coordinating endocrine, autonomic and behavioral responses to stressful stimuli. Benzodiazepines exert many effects which are antithetical to those of CRF, including anxiolysis and suppression of the pituitary-adrenal axis. Although there is evidence that benzodiazepines can modulate several electrophysiological and behavioral responses to exogenous CRF, we questioned whether this class of drug might also affect CRF biosynthesis as well. We have shown previously that footshock stress increases CRF mRNA levels as monitored by in situ hybridization histochemical techniques in the paraventricular nucleus (PVN) and Barrington's nucleus (the pontine micturition center). We report here the effects of the potent benzodiazepine, chlordiazepoxide (CDP), on stress-induced CRF mRNA accumulation in these two regions. Male albino rats were exposed to electrical footshock (1.5 mA, 1-s duration, 60 times/30 min) twice daily for 4 days and sacrificed 24 h after the last shock session. Either CDP (1, 2.5, 5 or 10 mg/kg) or saline was given i.p. 30 min before each stress. Sections were hybridized with an 35S-labeled prepro-CRF cRNA probe. Relative levels of CRF mRNA were quantified by densitometry of the autoradiography with X-ray film. CRF mRNA concentrations were significantly increased in both the PVN and Barrington's nucleus after stress, and CDP attenuated these increases in the PVN. By contrast, CDP did not affect CRF mRNA accumulation in Barrington's nucleus after stress. The results suggest that the benzodiazepine, CDP, suppresses stress-induced pituitary adrenal activation at least in part through inhibition of CRF production in the PVN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals,Chlordiazepoxide,Corticotropin-Releasing Hormone,Electroshock,Foot,In Situ Hybridization,Male,Paraventricular Hypothalamic Nucleus,RNA, Messenger,Rats,Rats, Sprague-Dawley,Stress, Physiological

241099,876354,918669,1149838,1488095,1612002,2002354,2159487,2804647,2809479,2858999,2871808,2884126,2981744,3023041,3027601,3037041,3072487,3081925,3285964,3498106,3871412,3927353,4155792,4294064,4988497,5575787,6104336,6112528,6117083,6267699,6280090,6289439,6314446,6383518,6601247,6603620,6605851,6681257,6787456,7193293,7357459,14340716

8221104

Attenuation of stress-induced behavior by antagonism of corticotropin-releasing factor receptors in the central amygdala in the rat.

Research suggests that endogenous corticotropin-releasing factor (CRF) in the amygdala plays a role in the expression of stress-induced behavior. This study examined in rats whether antagonism of CRF receptors in the central amygdala (CA) region using alpha-helical CRF9-41, a CRF antagonist, was effective in attenuating the occurrence of stress-induced freezing. Bilateral infusions of 50, 100, or 200 ng of the CRF antagonist were made in the CA region using 33-gauge cannula immediately prior to testing. Freezing was measured in two test conditions. In one condition, the effects of the CRF antagonist on freezing was assessed immediately after exposure to electric foot shock. In the other condition, freezing was examined in shock-experienced rats that were re-exposed to the shock environment. Results suggested that 50 and 100 ng of the CRF antagonist were effective in reducing the duration of freezing in the immediate post-shock period. In addition, the 100 ng dose produced a significant reduction in freezing duration after rats were re-exposed to the shock environment. Collectively, data suggest that antagonizing the action of endogenous CRF in the CA region contributes to a general alleviation of stress-induced freezing.

Amygdala,Animals,Behavior, Animal,Corticotropin-Releasing Hormone,Defense Mechanisms,Dose-Response Relationship, Drug,Male,Rats,Rats, Sprague-Dawley,Receptors, Corticotropin-Releasing Hormone,Stress, Physiological

1326376,1327398,1607942,1933327,1980834,2155045,2299391,2343163,2428439,2543357,2717061,2786722,2834018,2868027,3001239,3148150,3262400,3265790,3393697,3496511,3498816,6308694,6601247,6709778,6715573,6755288,6984756,14201838

8221105

Neurons in the area of human thalamic nucleus ventralis caudalis respond to painful heat stimuli.

A population of neurons in the area of human thalamic nucleus ventralis caudalis (Vc) respond to noxious heat stimuli. In the cutaneous core of Vc 6% (6/108) of recorded neurons had a significantly greater response to noxious heat stimuli than to innocuous control stimuli. Half of these neurons (n = 3) also responded to innocuous cold stimuli. Within the region posterior and inferior to the cutaneous core of Vc 5% (4/77) of neurons responded exclusively to noxious heat stimuli. Cells responding to noxious heat were recorded at a greater proportion (66%) of sites where painful sensations were evoked by microstimulation than at sites where nonpainful sensations were evoked (1.5%). The results suggest that neurons in the region of human Vc mediate the sensory aspect of pain.

Electric Stimulation,Electrophysiology,Hot Temperature,Humans,Movement Disorders,Neurons,Pain,Physical Stimulation,Sensory Thresholds,Thalamic Nuclei

110850,198724,411896,773595,1102064,1132234,1569463,1702464,1716595,1738568,2477421,2592598,2720229,2794144,3346719,3351564,3351591,3653318,3656204,3760926,4032311,4163109,4961088,4966615,4974746,6688662,6736292,6867738,7119862,7411178,7430431,8360716,8463817,13734415,13768983,14413792

8221106

Spontaneous activity in the thalamic reticular nucleus during the sleep/wake cycle of the freely-moving rat.

Neurons of the somatosensory thalamic reticular nucleus (TRN) were studied by extracellular recordings through the sleep/wake cycle in the unanesthetized, freely-moving rat. All electrophysiologically-identified TRN neurons expressed rhythmic patterns of discharge that altered with shifts in sleep/wake state. During slow wave (SW) sleep, neurons displayed spike-burst discharges in long trains followed by pauses. high-frequency oscillations in auto-correlograms in the spindle-frequency range (approximately 10 Hz) reflected the rhythm of interburst intervals within the trains whereas low-frequency oscillations (0.3-0.2 Hz) displayed the rhythm of intertrain intervals. During rapid eye movement (REM) sleep, a more continuous pattern of spike-burst discharges was prominent, resulting in absence of a detectable, low-frequency rhythm but persistence of spindle-frequency firing. At the transitions between SW and REM sleep, cell discharge was more tonic than during either sleep state and lacked a dominant rhythm. During the wake (AW) state, neurons fired in a single-spike mode that also lacked rhythmicity. Unlike their pattern of discharge, TRN neurons' mean rate of discharge did not distinguish sleep/wake state. The mean discharge rates were: SW, 18.4 +/- 1.3; REM, 17.4 +/- 1.2; AW, 22.3 +/- 2.1 (Hz +/- S.E.M.). Mean discharge rate during transitions from SW to REM sleep (28.6 +/- 2.1) was significantly higher, however, than during any sleep/wake state. Compelling evidence was lacking for segregation of TRN neurons into discrete populations according to absolute discharge rate. Neurons recorded simultaneously from the same electrode discharged synchronous trains of spike-bursts and pauses during SW sleep. This phenomenon may be related to generation of EEG slow waves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals,Electrophysiology,Periodicity,Rats,Rats, Inbred Strains,Sleep Stages,Sleep, REM,Thalamic Nuclei

1150923,1244990,1465191,1707896,1712843,1756835,1840071,1941080,2428443,2442206,2466060,2558172,2605506,2645620,2990981,3148691,3183710,3299139,3390708,3398922,3399055,3542127,3559675,3560000,3944624,4087044,4373534,5093726,5499817,6205857,6209310,6525241,6824942,7238704,7284786,7322350,7417821

8221107

Functional mapping of neural sites mediating prolactin-induced hyperphagia in doves.

Microinjections of prolactin (PRL) into the ventromedial nucleus of the hypothalamus (VMN) or the preoptic area (POA) have been previously shown to increase food intake and body weight in ring doves. In an attempt to corroborate these results and to provide a more complete map of PRL-sensitive brain sites mediating the orexigenic action of PRL, a microinjection procedure was employed in the present study that delivered PRL or saline vehicle in extremely small volumes (10 nl/injection) to a variety of diencephalic sites in dove brain that had been previously demonstrated to contain high concentrations of PRL receptors. Estimates obtained from one female subject given a single 10 nl injection of [125I]ovine PRL into the VMN supported the claim that such injection volumes resulted in limited diffusion, as 80% of the tissue radioactivity was found within a 280 mm area surrounding the injection site at 30 min after injection. Food intake of cannulated male doves in the mapping study was monitored daily during a 6 day baseline period, an initial 4 day treatment period, a 6-12 day post-treatment recovery period, and a second 4 day treatment period. Approximately half of the birds received PRL injections (50 ng/10 nl twice daily) and saine vehicle injections (10 nl twice daily) during the first and second treatment periods, respectively, while remaining birds received these treatments in the reverse order. No significant changes in food intake across baseline, vehicle, post-treatment, or PRL treatment periods were observed in birds with injection sites in the lateral POA, paraventricular nucleus of the hypothalamus (PVN), or the medial-basal hypothalamic region between the tuberal hypothalamus (TU) and VMN. In contrast, injections of PRL into the VMN area, medial POA, or TU resulted in average daily food intake values that significantly exceeded those recorded during other periods. The most robust feeding response was seen in the VMN group, where PRL injections resulted in a 58% increase in food intake over that recorded during injection of vehicle. This increase was significantly greater than that observed following PRL injections into the mPOA (26%) or the TU (32%). These findings suggest that the VMN may be a primary site of PRL action in promoting hyperphagia in this species, although PRL effects at other diencephalic loci, such as the mPOA and TU, may also contribute to the orexigenic action of this hormone.

Animals,Birds,Brain Mapping,Diencephalon,Eating,Feeding Behavior,Female,Hyperphagia,Hypothalamic Area, Lateral,Male,Preoptic Area,Prolactin,Ventromedial Hypothalamic Nucleus

810735,974767,1782544,1937430,2015361,2236014,2620072,2731045,2845312,2870773,3070587,3134673,3251237,3411283,3760743,3817448,3902150,4007798,4426995,4577101,4735146,4860715,5545725,6343908,7079336,7085935,7276801,7408952,8367036,8457858,13920110,14854036,19215404

8221108

Identification of periaqueductal gray and dorsal raphe nucleus neurons projecting to both the trigeminal sensory complex and forebrain structures: a fluorescent retrograde double-labeling study in the rat.

The midbrain periaqueductal gray (PAG) including the dorsal raphe nucleus (DR) has been known to contain serotoninergic neurons projecting to many brain regions. Employing fluorescent retrograde double labeling combined with immunofluorescence histochemistry for serotonin (5-HT), we examined in the rat whether or not single PAG/DR neurons with 5-HT send their axons to both the trigeminal sensory complex and forebrain regions. Stereotaxic injections of Diamidino Yellow (DY) and Fast Blue (FB) were performed unilaterally; DY was injected into the caudal spinal trigeminal nucleus or principal sensory trigeminal nucleus, and FB into the ventrolateral orbital cortex, nucleus accumbens or amygdala. A small percentage of PAG/DR neurons were doubly labeled with DY and FB, and the majority of them showed 5-HT-like immunoreactivity (5-HT-LI). Most of these 5-HT-LI PAG/DR neurons that were indicated to send their axons simultaneously to both the trigeminal sensory complex and forebrain regions were distributed in the ventrolateral PAG subdivision and ventral aspects of the medial PAG subdivision at the middle and caudal PAG levels, bilaterally with a predominant distribution on the side ipsilateral to the injections. This indicates a possible role of these PAG/DR neurons in the limbic or affective-motivational aspect of the pain-related neural system.

Amidines,Animals,Brain Mapping,Fluorescent Dyes,Male,Neurons,Periaqueductal Gray,Prosencephalon,Raphe Nuclei,Rats,Rats, Wistar,Synaptic Transmission,Trigeminal Nuclei

64477,77865,137766,205165,216303,565370,679048,714251,1118029,1354402,1383285,1467936,1506482,1638420,1674413,1705670,1710039,1738579,1747767,1783685,1815148,2657504,2834665,3022186,3282614,3486166,4044895,4549764,4887743,5167502,6132587,6143527,6164006,6166661,6257861,6663336,6757802,6854362,6854363,7028211,7298902,7683999,7687754,8327190

8221109

Neurons in the superficial dorsal horn of the rat spinal cord projecting to the medullary ventrolateral reticular formation express c-fos after noxious stimulation of the skin.

The nociceptive nature of the neurons of the superficial dorsal horn (laminae I-III) which project to the medullary ventrolateral reticular formation is studied in the rat. Medullary injections of Fluoro-Gold showed exclusive retrograde labeling of laminae I-III cells when the tracer filled a zone intermediate between the lateral tip of the lateral reticular nucleus and the spinal trigeminal nucleus, pars caudalis. This zone is here called VLMlat. Following noxious mechanical or thermal stimulation of the skin, double-labeled neurons, which stained retrogradely and were Fos-immunoreactive, prevailed in laminae I and IIo. Double-labeled neurons were few in lamina IIi after thermal stimulation and entirely lacking in lamina III after the two kinds of stimulation. Findings in lamina I confirm previous electrophysiological data (see Menétrey et al., J. Neurophysiol., 52 (1984) 595-611) showing that lamina I cells projecting to the ventrolateral reticular medulla convey noxious messages. The occurrence of numerous double-labeled cells in lamina IIo suggests that this lamina is also involved in nociceptive transmission to the VLMlat.

Animals,Fluorescent Dyes,Hot Temperature,Male,Medulla Oblongata,Neurons,Nociceptors,Pain,Physical Stimulation,Proto-Oncogene Proteins c-fos,Rats,Reticular Formation,Skin Physiological Phenomena,Spinal Cord,Stilbamidines,Synaptic Transmission

83245,84002,99460,228014,447881,710558,1504797,1705157,1721691,1722887,1724066,2215924,2425899,2462188,2503547,2594201,2731034,2858497,2870140,2887644,2913071,3112583,3214735,3722438,3840182,4044936,4131625,6162863,6197429,6491707,6512014,6643737,6877845,7085928,7137588,7400394,14168633

8221110

High metabolic activity demonstrated by positron emission tomography in human auditory cortex in case of deafness of early onset.

Glucose metabolism has been studied in the auditory cortex of human subjects with deafness of early onset, and compared to normal subjects with ears plugged. The metabolism in the auditory cortex and in the association auditory cortex was higher in deaf subjects than in normal subjects. This result is compared to similar observations that we made previously in the visual cortex of human subjects with blindness of early onset.

Adolescent,Adult,Analysis of Variance,Auditory Cortex,Brain,Deafness,Glucose,Humans,Male,Reference Values,Tissue Distribution,Tomography, Emission-Computed

117743,363301,450139,871928,880104,1554432,1556888,1573879,1724210,1825496,1851187,1997494,2083558,2322834,2341551,2583198,3370494,3909200,3952506,5574524,6331282,6605781,6927557,6978932,7093705,7359175,15408222

8221111

An analysis of GABAergic afferents to basket cell bodies in the cat's cerebellum.

An antibody to glutamic acid decarboxylase (GAD) was used to identify GABAergic terminals around the somata of basket cells in the cat's cerebellar cortex. Two sources for GAD immunoreactive terminals were identified based on size and cytological characteristics including the recurrent collaterals derived from Purkinje cells and the axons of stellate cells. The majority of the unlabeled terminals likely arise from parallel fibers. The present analysis indicates that GAD-positive terminals form 13% of the synaptic contacts on basket cells. The remaining 87% are unlabeled. Thus, GAD-positive terminals represent a small proportion of the synaptic input to basket cell bodies as compared to afferent endings that likely mediate excitation.

Animals,Cats,Cerebellar Cortex,Glutamate Decarboxylase,Granulocytes,Horseradish Peroxidase,Immunohistochemistry,Microscopy, Electron,Neurons, Afferent,Purkinje Cells,Synapses,gamma-Aminobutyric Acid

75042,92901,2723768,3066636,3385490,3528931,4854839,4866553,6255484,7153787,8250283,8250284

8221112

Loss of sigma binding sites in the CA1 area of the anterior hippocampus in Alzheimer's disease correlates with CA1 pyramidal cell loss.

The densities of [3H]1,3-di-o-tolylguanidine ([3H]DTG) binding to sigma binding sites in the CA1 stratum pyramidale region in 7 hippocampi affected by Alzheimer's disease, were compared with densities in 7 normal hippocampi. There was an average reduction of 26% in [3H]DTG binding in this area, which was correlated with an average 29% pyramidal cell loss in the same region. These results are consistent with experiments in animals indicating that sigma binding sites are preferentially associated with the somata of large cells.

Aged,Alzheimer Disease,Autoradiography,Binding Sites,Cell Death,Female,Guanidines,Hippocampus,Humans,Male,Receptors, sigma,Reference Values,Tissue Distribution

945347,1325354,1325359,1407551,1608537,1664275,1964225,1965859,2060604,2154780,2205507,2443073,2471324,2552073,2557123,2839797,2856948,2906878,2995073,3012017,3323927,3513895,6092969,6147851

8221113

L-dopa pretreatment potentiates striatal dopamine overflow and produces dopamine terminal injury after a single methamphetamine injection.

Rats receiving L-dopa/carbidopa (70 mg/kg/17.5 mg/kg, i.p.) 1 h prior to a single methamphetamine (m-AMPH) (4 mg/kg, s.c.) pretreatment showed an extraordinary striatal dopamine (DA) overflow into the extracellular space (30-60 times basal overflow) as compared to the DA overflow elicited by m-AMPH alone (4-5 times basal). Animals treated with L-dopa/carbidopa plus m-AMPH, but not m-AMPH alone, had substantial (60%) decreases in striatal DA content 1 week later. These findings support the conclusion that the magnitude of m-AMPH-induced DA overflow contributes to the degree of nerve terminal damage and highlight the importance of extracellular DA in striatal terminal damage.

Analysis of Variance,Animals,Chromatography, High Pressure Liquid,Corpus Striatum,Dialysis,Dopamine,Drug Synergism,Electrochemistry,Injections,Levodopa,Male,Methamphetamine,Nerve Endings,Nervous System,Rats,Rats, Sprague-Dawley

43481,216794,567274,1356579,1486494,1571078,1637067,1810626,2113413,2123121,2128125,2128499,2142010,2496196,4121370,6145488,6260009,6940202,8473897,14907713

8221114

Attenuation of cholinergic analgesia by nifedipine.

Nociception was tested in mice receiving oxotremorine or physostigmine either after the dihydropyridine calcium channel blocker nifedipine or the non-calcium antagonist vasodilator hydralazine. Nifedipine did not change the reaction time to thermal stimulation (tail-flick test), but attenuated the prolonging action on tail-flick latencies exerted by the two cholinomimetic agents. Hydralazine had no effect alone nor modified the action of cholinomimetics. The results suggest that attenuation of cholinergic analgesia by nifedipine might be related to not yet defined neuronal changes produced by calcium channel blockade, but changes in the pharmacokinetics of oxotremorine and physostigmine cannot be ruled out.

Analgesics,Animals,Hot Temperature,Hydralazine,Male,Mice,Mice, Inbred Strains,Nifedipine,Oxotremorine,Pain Measurement,Parasympathomimetics,Physostigmine,Reaction Time

1359066,1360534,1365644,1606505,2384131,2415829,2431429,2432656,2868525,3050628,3220117,3384008,3609138,3627284,3953299,6504960,6733471,7855184

8221115

Multiple opioid system involvement in the mediation of parasitic-infection induced analgesia.

Although parasite modification of host behaviour is well established, little is known about the mechanisms underlying such effects. The present study examined the relationships between subclinical infection with the enteric sporozoan parasite, Eimeria vermiformis, nociceptive responses and endogenous opioid systems in male mice. Infected mice displayed significant analgesia which increased through the prepatent period [oocyst formation (pre-infective); days 1-7 post-infection (PI)], reached a maximum with the onset of patency (onset oocyst shedding and infectivity; days 7-8 PI) and declined during patency (oocyst shedding), with response latencies declining to basal levels with the cessation of oocyst production and infectivity (day 15 PI). The increasing nociception during the prepatent period (day 4 PI) was associated with kappa opioid mechanisms, being reduced by the kappa antagonist, nor-binaltorphimine, and insensitive to either the delta antagonist, ICI 174,864, or the general, predominantly mu antagonist, naloxone. Maximum analgesia (day 7 PI) associated with the onset of patency (infectivity) was sensitive to both the kappa and mu antagonists, but insensitive to the delta antagonist, while the declining analgesia during patency (day 10 PI) was reduced by the mu and delta antagonists, but was insensitive to the kappa antagonist. These results indicate that mu, delta and kappa opioid systems are involved in the mediation of subclinical parasitic infection-induced analgesia and likely other associated parasite-induced modifications of host behaviour.

Analgesia,Animals,Coccidiosis,Endorphins,Enkephalin, Leucine,Host-Parasite Interactions,Male,Mice,Mice, Inbred Strains,Naloxone,Naltrexone,Narcotic Antagonists

967527,1309957,1387962,1846441,2234607,2536183,2571452,2678270,2832195,2839664,2882399,6094941,6245210,6323195,6512725,6709395,7175619,8385627,8410548,15463407

8221116

Interleukin-1 mediates the behavioral hyperalgesia produced by lithium chloride and endotoxin.

The sickness-inducing agents lithium chloride (LiCl) and lipopolysaccharide (LPS) produce a long-lasting facilitation of the nociceptive tailflick reflex. Many of the behavioral and physiological changes produced by illness are mediated by interleukin-1 (IL-1) released from monocytes stimulated by the pathogenic substance. Monocytes also produce an IL-1 receptor antagonist (IL-1ra) which has been sequenced and cloned. The present experiments report that IL-1 can itself produce hyperalgesia as assessed by tailflick to radiant heat, and that recombinant IL-1ra blocks the hyperalgesia produced by LiCl and LPS.

Animals,Behavior, Animal,Endotoxins,Hot Temperature,Hyperalgesia,Interleukin-1,Lipopolysaccharides,Lithium Chloride,Pain Measurement,Rats,Rats, Sprague-Dawley,Reaction Time,Tail

205165,1281746,1334766,1351668,1358641,1393581,1409612,1501774,1542935,1602402,1671393,1698365,1796497,1826616,1826945,1838480,1972388,2137201,2507329,2528582,2676681,3137474,3260869,3265161,3277884,6896839,7681556

8221117

L-dopa stimulates c-fos expression in dopamine denervated striatum by combined activation of D-1 and D-2 receptors.

Administration of L-dopa to unilaterally 6-hydroxydopamine-lesioned rats, activates the early gene c-fos in the lesioned caudate-putamen. D-1 receptor blockade by SCH 23390, prevented L-dopa-induced Fos-like immunoreactivity in the whole caudate-putamen, while D-2 receptor blockade by raclopride reduced Fos-like immunoreactivity only in the dorso-lateral portion. The results suggest that L-dopa induces c-fos primarily through an activation of D-1 receptors, while D-2 receptor stimulation plays a facilitatory influence on D-1-mediated c-fos expression.

Animals,Benzazepines,Corpus Striatum,Denervation,Dopamine,Dopamine D2 Receptor Antagonists,Levodopa,Male,Proto-Oncogene Proteins c-fos,Raclopride,Rats,Rats, Sprague-Dawley,Receptors, Dopamine,Receptors, Dopamine D1,Receptors, Dopamine D2,Salicylamides

1346165,1347406,1357113,1359451,1827915,1971013,2147780,2410769,2479148,2495972,2872071,2907616,2946360,2959833,6273735,8093571,8098138

8221118

Antibodies to quinolinic acid reveal localization in select immune cells rather than neurons or astroglia.

Polyclonal antibodies were produced against quinolinic acid. No immunoreactivity was observed in any cell type in carbodiimide-fixed brain tissue from control rats. When the antibodies were applied to carbodiimide-fixed spleen tissue, strong quinolinic acid immunoreactivity was observed in some cells with the appearance of macrophages and dendritic cells. These findings indicate an immune system origin for quinolinic acid, and implicate immune cells in excitotoxic CNS pathologies. These findings also raise the possibility that quinolinic acid is a unique cytokine in immune system signal transmission.

Animals,Antibodies,Astrocytes,Brain,Carbodiimides,Dendritic Cells,Fixatives,Immune System,Immunohistochemistry,Macrophages,Neurons,Quinolinic Acid,Rats,Spleen,Tissue Distribution

291064,1322853,1422788,1534219,1696582,1700844,1720144,1722952,1827495,2148832,2165523,2301926,2472189,2475209,2500976,2522807,2866466,2904493,2974127,3346732,6232146,6849138,8450195

8221119

Individual differences in the psychomotor effects of morphine are predicted by reactivity to novelty and influenced by corticosterone secretion.

Clinical observations show that individual vulnerability to the reinforcing properties of drugs plays an important part in the subsequent development of addition. In animals, individual vulnerability to psychostimulants has been found to be predicted by their locomotor response to novelty as well as their corticosterone response. Rats with a high locomotor response to novelty (High Responders or HR) relative to Low Responders (LR), show a higher sensitivity to both the psychomotor and reinforcing effects of psychostimulants and a longer lasting corticosterone secretion in response to stress. In this study, we addressed two main questions. First, does the locomotor response to novelty also predict the psychomotor effects of morphine? Second, do differences in corticosterone secretion underlie individual differences in the stimulant effects of morphine? We compared the locomotor response to morphine (2 mg/kg s.c.) in: (i) HR and LR rats with an intact hypothalamo-pituitary-adrenal (HPA) axis; (ii) HR and LR rats in which stress-induced corticosterone secretion was suppressed by adrenalectomy but basal levels of corticosterone were maintained by implantation of subcutaneous corticosterone pellets. In animals with an intact HPA axis, HR rats showed a higher locomotor response than did LRs to morphine. In animals in which corticosterone secretion was suppressed, the enhanced locomotor response of the HRs to morphine fell to that observed in the LRs. In conclusion our data show that, (1) individual reactivity to novelty can predict individual vulnerability to the psychomotor effects of opioids, and (2) stress-induced corticosterone secretion may play a role in determining individual differences in sensitivity to these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy,Analysis of Variance,Animals,Corticosterone,Exploratory Behavior,Forecasting,Individuality,Male,Morphine,Motor Activity,Psychomotor Performance,Rats,Rats, Sprague-Dawley

504396,530497,1321572,1380861,1486498,1525663,1726140,1821483,1986388,2006148,2351111,2409422,2682400,2781295,2879285,3021281,3059926,3698813,8448654,11175418,11224170

8221120

Increase of central 5-HT1B binding sites following 5,7-dihydroxytryptamine axotomy in the adult rat.

The effects of selective axotomy of serotoninergic neurons produced by an intracerebroventricular injection of 5,7-dihydroxytryptamine (200 micrograms free base) on 5-HT1B binding sites labeled with S-CM-G-[125I]TNH2 were investigated by quantitative autoradiography in the rat brain. Results show, 21 days after surgery, an upregulation of 5-HT1B receptors in the entorhinal cortex and the dorsomedial and suprachiasmatic nuclei of the hypothalamus. The cellular localization of those 5-HT1B receptors exhibiting post-lesion plastic properties is discussed.

5,7-Dihydroxytryptamine,Animals,Autoradiography,Axons,Binding Sites,Brain,Denervation,Hypothalamus,In Vitro Techniques,Injections, Intraventricular,Limbic System,Male,Rats,Rats, Sprague-Dawley,Receptors, Serotonin,Serotonin,Up-Regulation

732817,1504738,1738002,1836757,1852219,1913239,2138221,2420612,2862270,2936965,2947981,3335996,4052776,6884427,8159291,8431786,8495340,19210410,20493117

8221121

Hypoxia affects differently the intracellular pH of clustered and isolated glomus cells of the rat carotid body.

Clustered and isolated glomus cells, cultured from rat carotid bodies, were exposed to hypoxia (pO2 2-30 torr) induced by applications of sodium-dithionite (Na2S2O4). Hypoxia decreased or increased intracellular pH (pHi) of clustered cells about equally, but lowered it in most isolated cells. The levels of intracellular acidification were similar in both groups whereas alkalinization was more pronounced in the clusters. The H+ equilibrium potential (EH) and its changes during hypoxia (delta EH), were determined almost exclusively by pHi. Seventy-five percent of clustered cells became depolarized whereas 80% of isolated cells underwent hyperpolarization. In both groups, changes in the resting potential (delta EM) were directly and significantly correlated with delta EH, thus delta pHi. These observations support the view that clustered and isolated rat glomus cells behave differently. This difference may occur because of the presence (in the clusters) or absence (in isolated cells) of enveloping sustentacular cell processes.

Animals,Carotid Body,Cell Aggregation,Cell Polarity,Cell Separation,Dithionite,Hydrogen-Ion Concentration,Hypoxia,Intracellular Membranes,Membrane Potentials,Rats

457516,1294152,1504779,1629081,1665031,1815832,1884200,1933367,1980041,2061827,2247147,2475025,2759976,2852638,3419588,5837618,6434728,6758942,7679312,19605288

8221122

Morphology of CA3 neurons in hippocampal slices with nonepileptic and epileptic activity: a light and electron microscopic study.

In guinea pig hippocampal slices, relations between morphology and spontaneous bioelectric activity of neurons were studied in control saline and with exposure to the epileptogenic drug pentylenetetrazole (PTZ) for 2-3 h. Light and electron microscopic structures of the CA3 region were analysed after recording the membrane potential. Neurons in slices kept in control saline exhibited spontaneous aperiodic bioelectric activities partly mixed with rhythmically occurring burst discharges. In slices exposed to PTZ, these periodic burst discharges and/or paroxysmal depolarization shifts (PDS) predominated. Light microscopic comparison focussing on tissue preservation showed no significant differences between control and PTZ-treated slices. Ultrastructural morphology revealed, on the one hand, no differences regarding spine and synaptic densities, and on the other hand, significantly more irregular electron translucent vacuoles within dendrites of PTZ-treated slices being either randomly distributed or clustered. The vacuoles are interpreted as early changes during epileptic activity.

Animals,Epilepsy,Guinea Pigs,Hippocampus,Horseradish Peroxidase,In Vitro Techniques,Membrane Potentials,Microscopy, Electron,Neurons,Pentylenetetrazole,Pyramidal Tracts

487185,856951,2301927,2721612,3021508,3208089,3674798,3706028,3835581,4121704,4337350,4523024,5034855,6250666,6326943,6329464,6525239,6777154,6871737,6871738,6877491,6990707,7014911,7055738,7140893,7252134,7411185

8221123

Scopolamine injected into the rat amygdala impairs working memory in the double Y-maze.

Recent neurochemical results suggest the hypothesis that the nucleus basalis magnocellularis (nbm) cholinergic projection to the amygdala may play a role in memory. The present study investigated the effects of intra-amygdaloid injections of the cholinergic antagonist scopolamine on working and reference memory in the double Y-maze. Rats were pretrained until working and reference memory choice accuracy stabilized to a criterion of > or = 86% correct. Bilateral cannulae were then surgically implanted in the basolateral amygdaloid complex. Rats (n = 9) received scopolamine in doses of 8.0, 24.0, and 72.0 micrograms/0.5 microliter and saline (0.5 microliter) in a counterbalanced order with retraining to criterion between injections. Intra-amygdaloid scopolamine produced a dose-dependent and differential impairment of working and reference memory. A dose of 24.0 micrograms impaired working memory without significantly affecting reference memory; doses of 8.0 micrograms and 72.0 micrograms affected neither and both types of memory, respectively. Results implicate amygdaloid acetylcholine in memory.

Amygdala,Animals,Dose-Response Relationship, Drug,Habituation, Psychophysiologic,Learning,Male,Memory,Microinjections,Rats,Rats, Sprague-Dawley,Reward,Scopolamine

730861,1281523,1393607,1657298,1716012,1763188,1852317,1868359,1933423,1981091,2198869,2255401,2522306,2569316,2646552,2669837,2923657,3146771,3251239,3295586,3512630,3622683,3886715,3939663,4038997,4795498,6182963,6419260,14201838

8221124

Fornix degeneration and memory in traumatic brain injury.

Fornix-to-brain ratios (FBR) based on postinjury magnetic resonance (MR) studies were calculated on a group of 27 female traumatic brain injury (TBI) patients and 18 female medical controls by taking the widest aspect of the fornix at the level of the anterior horns and third ventricle and determining a fornix surface area. The FBR was significantly reduced in the TBI group (FBR = 0.1121) as compared to the normal control group (FBR = 0.1766). Despite these significant FBR findings indicating prominent atrophic changes of the fornix in TBI patients, the FBR did not relate systematically to neuropsychological outcome. These findings clearly indicate fornix vulnerability in TBI and that current quantitative MR methods are sensitive enough to detect such changes. However, fornix degeneration constitutes only one of many contributing factors to the anatomic basis of TBI-induced cognitive disturbances, as fornix atrophy did not relate systematically to neuropsychological outcome.

Adolescent,Adult,Atrophy,Brain,Brain Injuries,Female,Humans,Limbic System,Magnetic Resonance Imaging,Wounds and Injuries

1082559,1436522,1536638,1640954,1782534,2352026,2779190,3745416,7159060

8221125

Glucocorticoids regulate the development of intracellular signaling: enhanced forebrain adenylate cyclase catalytic subunit activity after fetal dexamethasone exposure.

Although glucocorticoids cause growth retardation and interfere with cell development, selective promotion of some aspects of cell function also has been reported. The current study examines whether glucocorticoids enhance intracellular transduction mechanisms mediated by adenylate cyclase in the developing forebrain, a region in which steroids have been shown to interfere with cell replication, maturation, and growth. Pregnant rats were given dexamethasone at doses spanning the threshold for growth impairment (0.05, 0.2, and 0.8 mg/kg) on gestational days 17, 18, and 19, and development of adenylate cyclase was evaluated in membrane preparations, using four different activity measures; basal adenylate cyclase in the absence or presence of GTP, maximal G-protein activation by fluoride in the presence of GTP, and stimulation mediated by forskolin-Mn2+, which bypasses the G-proteins. Prenatal exposure to dexamethasone produced a dose-dependent impairment of body growth, with smaller deficits in forebrain weights (brain sparing) indicative of systemic toxicity. Basal adenylate cyclase activity was unaffected by dexamethasone treatment, regardless of whether GTP was present in the assay. Similarly, fluoride stimulation developed normally in all dexamethasone groups. However, forskolin-Mn(2+)-stimulated activity was significantly enhanced in a dose-dependent fashion. These results suggest that glucocorticoids serve as positive factors for the development of adenylate cyclase catalytic subunit activity, independently of their adverse effects on general growth and development; thus, these hormones may be a primary regulator of cell signaling during early development.

Adenylyl Cyclases,Aging,Analysis of Variance,Animals,Body Weight,Colforsin,Dexamethasone,Female,Fluorides,GTP-Binding Proteins,Gestational Age,Guanosine Triphosphate,Macromolecular Substances,Maternal-Fetal Exchange,Membrane Proteins,Pregnancy,Prosencephalon,Rats,Rats, Sprague-Dawley,Weight Gain

184091,236560,570873,1111550,1318378,1337750,1353311,1391259,1500634,1641811,1657219,1667405,1882125,1908646,1966107,1966109,2048038,2174490,2177130,2414792,2444697,2498878,2545859,2602033,2623631,2699325,2842565,3028083,3031559,3174289,4703791,6112174,6256527,6268630,6278007,6292395,6466749,6894063,7353531,7452971,8211822,14907713

8221126

The pathway responsible for EEG synchronization and effect of histamine on this system.

Electrical stimulation (3 Hz, 0.5 volts) to the midbrain reticular formation of conscious rats induced significant increase of EEG power densities (synchronization) recorded at the frontal cortex (FCOR), nucleus ventralis thalami (VE), or nucleus medialis centralis thalami (CM). Significant synchronization was also observed in the FCOR when electrical stimulation was applied to the VE and CM. When ipsilateral and bilateral VEs were electrocoagulated, no EEG synchronization was observed in the FCOR and CM. Intracerebroventricular administration of histamine (Hi) caused a marked suppression of FCOR EEG synchronization in both CM-lesioned and normal rats through H1 receptors. EEG synchronization in FCOR was not induced in ipsilateral or bilateral VE-lesioned rats after RF stimulation. When Hi (1 microgram) was injected into the VE of normal rats, EEG synchronization of FCOR was markedly reduced after RF or VE stimulation. No such changes were induced when Hi was injected into the CM.

Animals,Cerebral Cortex,Cerebral Ventricles,Electric Stimulation,Electrocoagulation,Electroencephalography,Functional Laterality,Histamine,Injections, Intraventricular,Male,Microinjections,Rats,Rats, Wistar,Reticular Formation,Thalamic Nuclei

1696363,2169324,2416786,2565152,3841102,3968225,4105873,4918146,5333759,6489867,7096629,14129767,18421831,18421835

8221127

Neurotensin-induced hypothermia prevents hippocampal neuronal damage and increased locomotor activity in ischemic gerbils.

Hypothermia induced by surface cooling has shown to protect vulnerable regions of the brain during an ischemic insult. This study evaluated the neuroprotective efficacy of neurotensin, a potent hypothermic agent, using a 5-min carotid occlusion procedure in the gerbil. In Experiment 1, the dose-response and time course of neurotensin-induced hypothermia were evaluated (n = 5/dose). Central infusion of 10, 20, and 30 micrograms neurotensin were found to significantly decrease core body temperature of conscious gerbils within 30 min of administration. In Experiment 2, gerbils pretreated with 30 micrograms neurotensin were permitted to become hypothermic or were maintained at 37 degrees-38 degrees C (rectal) during ischemic insult. Other gerbils were pretreated with peptide vehicle prior to ischemic insult (at 37 degrees -38 degrees C) or underwent a sham procedure (n = 6/condition). At 24 h after surgery, gerbils were tested for increased locomotor activity in an open-field apparatus. Gerbils pretreated with peptide vehicle or neurotensin and maintained at 37 degrees-38 degrees C during ischemia had significantly higher activity levels compared to the other treated groups. In contrast, gerbils made hypothermic with neurotensin exhibited activity levels similar to sham gerbils. Histological assessment revealed that neurotensin-induced hypothermia protected the CA1 region from ischemic damage.

Analysis of Variance,Animals,Female,Gerbillinae,Hippocampus,Hypothermia,Ischemic Attack, Transient,Male,Motor Activity,Neurons,Neurotensin,Pyramidal Tracts

119233,1324251,1521147,1922950,1931486,2072098,2085736,2101081,2264078,2329123,2568705,2771174,3062474,3693428,3749297,4745447,5726746,7093691,7291042,14771796

8221128

Elevation of hippocampal extracellular acetylcholine levels by methoctramine.

Previous studies suggest that m2 muscarinic receptors serve as presynaptic autoreceptors. Blocking these receptors by selective antagonists may, therefore, lead to increased acetylcholine (ACh) release. This study assessed changes in extracellular ACh levels, via in vivo microdialysis, following administration of the m2 antagonist methoctramine. Drug or placebo (Ringer's solution) was perfused via a microdialysis probe into the CA1 hippocampal region of unrestrained, awake male Fischer rats. HPLC-EC was used for online analysis of the dialysates. Methoctramine significantly enhanced ACh release in a dose-dependent fashion as compared to placebo for the doses employed (0.25-16 microM). The present in vivo data corroborate studies that show increased ACh levels in vitro following application of m2 antagonists.

Acetylcholine,Analysis of Variance,Animals,Diamines,Dose-Response Relationship, Drug,Extracellular Space,Hippocampus,Kinetics,Male,Microdialysis,Parasympatholytics,Rats,Rats, Inbred F344,Stereotaxic Techniques,Time Factors

1690270,1784606,1852264,1871189,2188581,2400933,2443145,2549449,2625133,2804636,3214752,3335998,3436364,3559565,3992249,4078746,6141277,7350532

8221129

Brain angiotensin AT-2 receptor antagonism and water intake.

Intracerebroventricular administration of the angiotensin AT-2 receptor antagonist, PD 123319, inhibited drinking induced in rats by hypertonic NaCl, carbachol, isoproterenol, hypovolemia, and water deprivation, but had no effect on food intake. In contrast, the AT-1 antagonist, losartan potassium, had no effect on these intakes. A model of thirst is presented that incorporates an AT-2 receptor in a final common pathway for drinking.

Angiotensin Receptor Antagonists,Animals,Biphenyl Compounds,Carbachol,Cerebral Ventricles,Drinking Behavior,Imidazoles,Injections, Intraventricular,Isoproterenol,Losartan,Male,Models, Neurological,Pyridines,Rats,Rats, Sprague-Dawley,Tetrazoles

1311103,1393612,1515929,1521162,1584339,1605566,1858948,1933441,6486775,8451266

8221130

Streptozotocin-induced diabetes blocks the positive feedback release of luteinizing hormone in the female rat.

The effects of streptozotocin-induced (STZ) diabetes on the release of gonadotropins was studied in female rats. In the first experiment, rats were ovariectomized and 2 days later were injected with STZ. Three weeks later rats were treated with estrogen and progesterone and blood samples were taken via intraatrial cannulae for luteinizing hormone (LH) assay. Afternoon surges of LH were seen in 4/5 control but 0/8 STZ rats. Pituitary responses to LH-releasing hormone in vitro did not differ. In the 2nd experiment, ovariectomized estrogen-primed rats were killed prior to and during a progesterone-induced LH surge. As in Experiment 1, STZ-treatment inhibited the LH surge but did not effect the afternoon rise in median eminence norepinephrine turnover which has previously been shown to be important in stimulating LH release. Turnover of norepinephrine in the anterior hypothalamus was depressed in the diabetic rats both prior to and during the expected time of the LH surge. Dopamine turnover was depressed in all three brain regions studied. It can be concluded that the positive feedback control of LH release is severely attenuated in diabetic rats but the mechanism explaining the loss is not clear. Diabetes-induced alterations in hypothalamic catecholamine metabolism may be involved but further work is needed to more carefully define these relationships.

Animals,Anterior Hypothalamic Nucleus,Circadian Rhythm,Diabetes Mellitus, Experimental,Dopamine,Estradiol,Feedback,Female,Follicle Stimulating Hormone,Gonadotropin-Releasing Hormone,Hypothalamus,Hypothalamus, Middle,Luteinizing Hormone,Median Eminence,Norepinephrine,Ovariectomy,Pituitary Gland,Progesterone,Rats,Rats, Sprague-Dawley,Reference Values

454758,744054,1093914,1681439,1973672,2522388,2946568,3105612,3124773,3899819,3920097,4823910,6120832,6139760,6360674,6403566,6785074,6788717,6991277,7025943,7102763

8221131

Angiotensin II binding in area postrema and nucleus tractus solitarius of SHR and WKY rats.

The distribution of angiotensin II (AII) binding sites in the area postrema (AP) and adjacent nucleus tractus solitarius (NTS) was compared in spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats. 125I[Saralasin-1-Isoleucine8]-Angiotensin II (125I[SI]-AII) binding density was quantitated from autoradiographic images by computer-assisted image analysis. Seventeen 30 microns serial coronal sections inclusive of the entire AP were analyzed as either individual sections or as groups of sections designated as caudal, middle, or rostral area postrema regions. 125I[SI]-AII binding density was greatest in caudal AP and declined progressively in the rostral direction in both strains; however, binding density in SHR was significantly higher than in WKY rats at each level of the AP analyzed. 125I[SI]-AII binding in the entire area postrema was approximately 46% higher in SHR rats. In the NTS, however, there were no differences in binding density between strains. At the middle level of the AP, 125I[SI]-AII binding was highest in the ventral midline and lowest in the dorsolateral region. In the NTS, the highest 125I[SI]-AII binding density was found in the pars commissuralis and pars medialis. In conclusion a) 125I[SI]-AII binding density was nonhomogeneous in the AP and NTS of both strains, b) qualitatively similar patterns of nonhomogeneity of binding in the AP and NTS were noted in both strains; however, c) the SHR strain consistently had higher density AII binding than WKY in AP, but not in NTS.

Angiotensin II,Animals,Autoradiography,Binding Sites,Cerebral Ventricles,Iodine Radioisotopes,Male,Medulla Oblongata,Organ Specificity,Rats,Rats, Inbred SHR,Rats, Inbred WKY,Receptors, Angiotensin

851205,928763,1555867,1986946,1987323,2282500,2337823,2403363,2544109,2713673,2714009,2836110,2909296,2912220,2931031,2939351,2982457,3006878,3026859,3183366,3351297,3557601,3562315,3598591,3628083,3676761,3752268,3762929,3779450,3865191,3946636,3947969,4321187,6089597,6173102,6311736,6324205,6398134,7156231,14097352,20492915

8221132

The effect of insulin on norepinephrine uptake by PC12 cells.

We have previously reported that insulin can enhance endogenous noradrenergic activity in vitro in the rat CNS. In the present study, we examined one potential mechanism underlying this effect: the ability of insulin to inhibit norepinephrine (NE) reuptake and secondarily increase its synaptic concentration. Acute (20 min) insulin treatment (0.1-10 nM) significantly inhibited specific 3H-norepinephrine uptake by rat hypothalamic slices. To ascertain whether this is a direct effect of insulin on cells that can synthesize and release norepinephrine, we studied NE uptake by the rat pheochromocytoma PC12 cell line. In PC12 cells, insulin (0.5-10 nM) inhibited NE uptake whereas the related peptide, insulin-like growth factor 1 (IGF-1), did not. Insulin did not compete with 3H-mazindol (a ligand for the NE reuptake transporter) binding to PC12 cell membranes. Thus, this effect of insulin is not due to interaction with either IGF-1 receptors or the norepinephrine transporter, but may be due to insulin interaction with its own receptor. Chronic (96-h) insulin treatment of PC12 cells also resulted in an inhibition of 3H-norepinephrine uptake, and membranes prepared from cells chronically treated with insulin bound less 3H-desipramine than control membranes. Thus, chronic insulin treatment may result in a decrease in the numbers of membrane-associated transporters. We conclude that insulin has a direct and physiological role in the modulation of synaptic norepinephrine levels by modulating reuptake by cells that synthesize and release norepinephrine.

Animals,Binding Sites,Biological Transport,Cell Membrane,Desipramine,Dose-Response Relationship, Drug,Hippocampus,Hypothalamus,In Vitro Techniques,Insulin,Insulin-Like Growth Factor I,Kinetics,Male,Mazindol,Norepinephrine,PC12 Cells,Rats,Rats, Wistar

560237,639260,1065897,1653632,1689379,1712313,1762695,1996343,2008212,2514006,2549192,2855490,2869102,2969324,3282875,3292965,3542120,3762739,3821933,3896761,6254391,6284779,6339003,6466664,6514010,8448653

8221133

Melatonin reduces dopamine content in the neurointermediate lobe of male Syrian hamsters.

The effect of daily late afternoon administration of melatonin on the in situ activity of tyrosine hydroxylase (TH) was studied in the posterior pituitary (neurointermediate lobe) of the male Syrian hamster. After 3 weeks of melatonin administration, TH activity was significantly reduced in the posterior pituitary. This was associated with a significant decrease in norepinephrine (NE) content. After 5 weeks, TH activity and NE content were no longer significantly different from controls. Dopamine (DA) content of the posterior pituitary was decreased progressively by melatonin administration, with a reduction of greater than 50% after 5 weeks of treatment. These data provide evidence that melatonin has a potent inhibitory effect on the regulation of the dopaminergic system of the neurointermediate lobe--an effect that appears unrelated to changes in axonal TH.

Analysis of Variance,Animals,Cricetinae,Dopamine,Levodopa,Male,Melatonin,Mesocricetus,Norepinephrine,Organ Size,Pituitary Gland, Posterior,Testis,Time Factors

30997,1028951,1033827,1036241,1334003,1656299,1756377,1922678,2162381,2171920,2539234,3086765,6263600,6656879,7127086,7358120,14279179

8221134

Effects of intra-PVN injections of d- and l-norephedrine on feeding in rats.

Phenylpropanolamine (PPA) is thought to inhibit feeding by activation of alpha 1-adrenergic receptors within the paraventricular hypothalamus (PVN). Systemic injections of the PPA component enantiomers, d- and l-norephedrine (NEP), result in differential suppression of feeding (l-NEP more potent than d-NEP). Whether the norephedrine racemates induce differential anorexia subsequent to injection into the PVN is unknown. In the present study, adult male rats received intra-PVN injections of the d- and l-norephedrine enantiomers (0, 80, 160, and 240 nmol). Significantly greater anorexia was obtained for l-NEP relative to d-NEP. These results document a stereospecific effect of the norephedrine enantiomers within the PVN in inhibiting food intake and suggest that the interaction of these enantiomers with PVN alpha 1-adrenoceptors may mediate the similar difference in potency noted for systemic injections of d- and l-norephedrine.

Animals,Anorexia,Dose-Response Relationship, Drug,Feeding Behavior,Male,Microinjections,Norepinephrine,Paraventricular Hypothalamic Nucleus,Rats,Rats, Sprague-Dawley,Stereoisomerism

1309478,1350985,1356275,1617447,1678528,1687767,1837207,2224544,2320656,2845312,2881994,2995083,3556402,3703896,3905334,6246501,6277425,6300645,7098772

8221135

Mating-induced increases in FOS protein in preoptic area and medial amygdala of cycling female rats.

Genitosensory stimulation received during mating initiates neural and endocrine changes necessary for pregnancy. The present study examined sites of induction of the proto-oncogene, c-Fos, after mating in the cycling female rat to determine neural sites activated by such stimulation that might be involved in pregnancy initiation. Two groups of cycling female rats were exposed to males on the evening of proestrus and remained with the male until receiving either 14 mounts-with-intromission including ejaculations (Intromissions) or a control number of mounts-without-intromission (Mounts-Only). These two mating treatments were previously shown to induce pregnancy/pseudopregnancy in 100% and 0% of the animals, respectively. Seventy-five minutes after mating, females were perfused intracardially with 2% paraformaldehyde/2.5% acrolein, and the brains were processed for FOS immunocytochemistry using standard procedures. FOS-immunoreactive cells (FOS-IR) were counted in standard template quadrilaterals in the preoptic area (POA), medial amygdala (mAMYG), and the paraventricular (PVN), ventromedial (VMN), and dorsomedial (DMN) nuclei of the hypothalamus at 50 x magnification using a camera lucida. Significantly higher numbers of FOS-IR cells were seen in Intromissions females above Mounts-Only females in the POA and mAMYG, demonstrating that c-Fos expression in these areas depended upon cervical-vaginal stimulation rather than on cutaneous somatosensory input received in Mounts-Only tests. The cells within the POA and mAMYG that are activated in response to the intromittive stimulus may be directly involved in pathways triggering one or several of the neuroendocrine responses to mating in the female rat.

Amygdala,Animals,Estrus,Female,Nerve Tissue Proteins,Pregnancy,Preoptic Area,Prolactin,Proto-Oncogene Proteins c-fos,Rats,Secretory Rate,Sexual Behavior, Animal

1312199,1436507,1667903,1690635,1727695,1761754,1810635,1822561,1831888,1842702,1903243,1954900,2106097,2106434,2111893,2512584,2691387,2909362,3112583,3340269,5542775,5892200,6132586,6339213,6860975,7188747,7308135,7466382