bluuebunny/crossref_metadata_2025 huggingface dataset:
Topographically specific hippocampal projections target functionally distinct prefrontal areas in the rhesus monkey
Authors: Barbas Helen , Blatt Gene J.
Published: January 2005

The sources of ipsilateral projections from the hippocampal formation, the presubiculum, area 29a‐c, and parasubiculum to medial, orbital, and lateral prefrontal cortices were studied with retrograde tracers in 27 rhesus monkeys. Labeled neurons within the hippocampal formation (CA1, CA1′, prosubiculum, and subiculum) were found rostrally, although some were noted throughout the entire rostrocaudal extent of the hippocampal formation. Most labeled neurons in the hippocampal formation projected to medial prefrontal cortices, followed by orbital areas. In addition, there were differences in the topography of afferent neurons projecting to medial when compared with orbital cortices. Labeled neurons innervating medial cortices were found mainly in the CA1′ and CA1 fields rostrally, but originated in the subicular fields caudally. In contrast, labeled neurons which innervated orbital cortices were considerably more focal, emanating from the same relative position within a field throughout the rostrocaudal extent of the hippocampal formation.

In marked contrast to the pattern of projection to medial and orbital prefrontal cortices, lateral prefrontal areas received projections from only a few labeled neurons found mostly in the subicular fields. Lateral prefrontal cortices, lateral prefrontal cortices received the most robust projections from the presubiculum and the supracallosal area 29a‐c. Orbital, and to a lesser extent medial, prefrontal areas received projections from a smaller but significant number of neurons from the presubiculum and area 29a‐c. Only a few labeled neurons were found in the parasubiculum, and most projected to medial prefrontal areas.

The results suggest that functionally distinct prefrontal cortices receive projections from different components of the hippocampal region. Medial and orbital prefrontal cortices may have a role in long‐term mnemonic process similar to those associated with the hippocampal formation with which they are linked. Moreover, the preponderance of projection neurons from the hippocampal formation innervating medial when compared with orbital prefrontal areas followed the opposite trend from what we had observed previously for the amygdala (Barbas and De Olmos [1990]) (J Comp Neurol 301:1–23). Thus, the hippocampal formation, associated with mnemonic processes, targets predominantly medial prefrontal cortices, whereas the amygdala, associated with emotional aspects of memory, issues robust projections to orbital limbic cortices. Lateral prefrontal cortices receive robust projections from the presubiculum and area 29a‐c and sparse projections from the hippocampal formation. These findings are consistent with the idea that the role of lateral prefrontal cortices in memory is distinct from that of either medial or orbital cortices. The results suggest that signals from functionally distinct limbic structures to some extent follow parallel pathways to functionally distinct prefrontal cortices. © 1995 Wiley‐Liss, Inc.
Neurotransmitter receptors, endocrine responses and the biological substrates of depression: A review
Authors: Leonard B. E.
Published: January 2005

This review attempts to assess critically the evidence which implicates a disorder of CNS neurotransmission in the aetiology of depression. Evidence for such a disorder has been obtained from changes in neuroendocrine function and in the activity of neurotransmitter receptors located on platelets and lymphocytes of depressed patients. Such studies are important not only because they give an insight into the possible biochemical basis of the illness, but also because they may be used as markers for the onset of depression and of response to treatment. The review concludes with a brief assessment of the change in immune responsiveness which may be associated with the onset of depression. Such studies support the view that the biological changes occurring in depression are not restricted to the brain and therefore open up the possibility that biochemical tests based on analysis of a blood sample may form a useful adjunct to clinical assessment.
Erythrocyte folate before and during treatment with lithium
Authors: Schou Mogens , Mortensen Esper , Vestergaard Per
Published: January 2005

We determined erythrocyte folate in normal subjects (blood donors) as well as in manic‐‐depressive patients before the start of prophylactic lithium treatment and at various times during the treatment. Before treatment the patients' erythrocyte folate was 25 per cent lower and after 6 months of treatment it was 10 per cent lower than the control value. Thereafter patient values and control values did not differ. Lithium treatment accordingly normalised on abnormal folate balance, but it is also possible that lithium in itself may have elevated erythrocyte folate. This is supported by animal data. Rats were given ordinary food and food containing lithium. After eight weeks erythrocyte folate was 27 per cent higher in the lithium‐treated rats than in the controls. Our study does not support the notion that folate supplements are required during lithium therapy.
Lithium longitudinally: An analysis of publication frequencies
Authors: Schou Mogens
Published: January 2005

This paper describes a longitudinal analysis of the frequency of publications over the period 1850–1984 about the biology, the pharmacology and the clinical use of lithium. Distinct phases reflect the various uses of lithium – antimanic, prophylactic and medical – but also reveal concern about unwanted effects, interest in mode of action, and search for valid alternatives.
Lithium and neuroleptics in the management of manic depressive psychosis
Authors: Lowe M. R. , Batchelor D. H.
Published: January 2005

The history of the use of combined lithium and neuroleptics in manic depressive psychosis can be traced from more than 30 studies published over the last 35 years in patients mainly described as suffering from schizo‐affective illness. DSM IIIR identifies one sub‐type of schizo‐affective disorder–schizoaffective disorder bipolar type–which may predict a good response to combined lithium and neuroleptic therapy. Whilst lithium and oral neuroleptics are widely prescribed, little attention has been paid to the use of depot neuroleptics. Haloperidol decanoate, used alone or in combination with lithium for up to 85‐months has proved to be acceptable and effective prophylactic therapy for some unstable manic depressive patients.
Effects of single doses of alprazolam and alcohol alone and in combination on psychological performance
Authors: Bond A. , Silveira J. C. , Lader M.
Published: January 2005

The effects of alprazolam l mg alone and in combination with 0·5 g/kg of alcohol for males and 0·42 g/kg for females were examined on a range of psychological tasks 90 and 180 min post‐drug (45 and 135 min post‐alcohol). Forty‐eight healthy volunteers were assigned randomly to four independent groups who received: alprazolam and placebo drink, alprazolam and alcohol, placebo capsule and alcohol, placebo capsule and placebo drink, respectively. Alprazolam caused subjective sedation, unsteadiness, dizziness and physical tiredness and impaired performance on all tasks. Alcohol caused similar subjective effects but little objective impairment. The effects of the combination were generally no greater than predicted from the sum of the single effects.
The effect of acute alcohol intoxication on psychometric testing and 5‐HT‐induced platelet aggregation in normal subjects; modulatory role of evening primrose oil
Authors: Corbett R. , Meagher J. B. A. , Leonard B. E.
Published: January 2005

Groups of university students were exposed acutely to alcohol (100 ml vodka) and their performance in the Bexley Maudsley Automated Psychological Screening Tests (BMAPS) was assessed. Blood samples were also taken to assess platelet aggregation to 5‐HT challenge. After 1 week administration of Evening Primrose Oil (EPO) or placebo under double‐blind conditions the students were re‐assessed. No mean difference was found in the psychometric testing of any of the groups either before or after the administration of EPO; however 5‐HT‐induced platelet aggregation was significantly potentiated in those groups exposed to alcohol, and was further increased in the group receiving EPO. These results suggest that platelet aggregation in response to 5‐HT is more sensitive than psychometric tests commonly used to assess alcoholism in detecting changes due to acute alcohol intoxication.
Effects of price, ‘openness’ of the economy and magnitude of the alternative reinforcer on responding for caffeinated coffee
Authors: Mitchell Suzanne H. , Laurent Carol L. , De Wit Harriet , Zacny James P.
Published: January 2005

Consumption of a commodity is influenced by various factors. This experiment examined three factors: unit price, ‘openness’ of the economy, and magnitude of an alternative reinforcer. Subjects earned caffeinated coffee and money by responding on concurrent random‐ratio (RR) schedules. Coffee price was varied by changing the coffee schedule from RR 1·3 to RR 16, while holding the money schedule constant (RR4). Openness of the economy was varied by changing the amount of unearned coffee provided during a 2‐h post‐task period (0, 1·5 or 3 free cups). The magnitude of the alternative reinforcer was varied by allowing subjects to earn an average of $2·00 or $6·00 for responding on the money schedule. Number of responses for coffee and amount of coffee earned varied inversely with the openness of the economy, but were unaffected by the amount of money available. Analysing the demand for coffee as a function of coffee price revealed that coffee was a less elastic commodity when the economy was closed than when it was more open. Within the range of parameters tested here, price of caffeinated coffee and openness of the economy strongly affected responding in humans, whereas the magnitude of an alternative monetary reinforcer had only limited effects.
Fluvoxamine augmentation in chronic schizophrenia: An open exploratory study
Authors: Silver Henry , Kaplan Alla , Kushnir Mina
Published: January 2005

The effect of augmenting standard antipsychotic treatment with the specific serotonergic reuptake inhibitor (SSRI) fluvoxamine was examined in severely disabled chronic schizophrenic inpatients using an open, naturalistic protocol. Fluvoxamine in doses ranging from 25 to 200 mg was added to the antipsychotic medication which was kept constant. Patients were followed for the duration of treatment (to date up to 7·5 months). Assessment included BPRS SANS SAPS and CGI scales (CGI only in the most severely disturbed), and global impressions of occupational and social functioning. Fourteen (74%) of the 19 patients studied showed improvement using 15 per cent change in SANS score or CGI improvement score > = 1 as criterion. The symptom constellation appeared to influence the rate and timing of response. Ten patients experienced exacerbations, some within 2 months of starting treatment, others after 5–6 months. The findings suggest that SSRI augmentation may be effective in severely disabled schizophrenics.
Alteration in the IL‐2 signal peptide affects secretion of proteins in vitro and in vivo
Authors: Zhang Lei , Leng Qixin , Mixson A. James
Published: January 2005

Background

Although hundreds of different signal peptides have now been identified, few studies have examined the factors enabling signal peptides to augment secretion of mature proteins. Signal peptides, located at the N‐terminus of nascent secreted proteins, characteristically have three domains: (1) a basic domain at the N‐terminus, (2) a central hydrophobic core, and (3) a carboxy‐terminal cleavage region. In this study, we investigated whether alterations in the basic and/or the hydrophobic domains of a commonly used signal peptide from interleukin‐2 (IL‐2) affected secretion of two proteins: placental alkaline phosphatase (AP) and endostatin.

Methods

A series of modifications in the basic and/or hydrophobic domains of the IL‐2 signal peptide were made by polymerase chain reaction with endostatin or AP plasmids as templates. Transfection of wild‐type or modified IL‐2 signal peptides fused in‐frame with endostatin or AP were done with Superfect in vitro or by the hydrodynamic method in vivo.

Results

Increasing both the basicity and hydrophobicity of the signal peptide augmented the secretion of AP and endostatin by approximately 2.5‐ and 3.5‐fold, respectively, from MDA‐MB‐435 cells in vitro. Over a range of DNA concentrations and times, the most effective IL‐2 signal peptide increased AP levels in the medium compared to the wild‐type IL‐2 signal peptide. Comparable results from these modified IL‐2 signal peptides were found to increase AP levels in the medium from bovine aortic endothelial cells. Moreover, the combined changes in basic and hydrophobic domains of the IL‐2 signal peptide augmented serum levels of endostatin and placental AP by 3‐fold when the optimal plasmid constructs were injected in vivo.

Conclusions

Modification of the IL‐2 signal peptide augments protein secretion both in vitro and in vivo. As a result, optimizing the signal peptide should be considered for increasing the therapeutic levels of secreted proteins. Copyright © 2004 John Wiley & Sons, Ltd.
Selective changes in the permeability of the blood‐brain barrier after pharmacological or surgical deafferentation
Authors: Walker Judith Boas , Walker James Paul , Bondy Stephen C. , Purdy Janet
Published: January 2005

Unilateral eye removal results in an increased delivery of blood‐borne glucose, norepinephrine, choline, and tyrosine, but not of proline, to the denervated optic lobes. Administration of reserpine to chicks increases penetrance of norepinephrine into the brain but not of tyrosine, choline, or proline. Selective alterations in the permeability of the blood‐brain barrier may represent a mechanism for the modulation of the delivery of critical nutrients to the brain.
A durable chronic unit recording device with movable microelectrode
Authors: Fernáandez‐Bueno Carlos , Lombillo Juan M. , Keene James J.
Published: January 2005

The design of a durable chronic unit recording device with movable microelectrode suitable for cats and monkeys is presented. Sufficiently rugged to remain on cats for weeks during exploration of a single electrode tract, the device also features: choice of stereotaxic coordinates over a large horizontal area at recording time; good stereotaxic precision; capability to hold a single unit for days; excellent insulation between the recording circuit and the animal; and simplicity of design and materials which allows fabrication of numerous devices in one lab.
Regional neurochemical studies on the effect of β,β′ ‐iminodipropionitrile (IDPN) in the rat
Authors: Langlais P. J. , Huang P. C. , Gabay S.
Published: January 2005

A permanent hyperkinetic syndrome, characterized by excitation, choreiform head and neck movements and circling, which has led to it being called collectively the “ECC‐syndrome,” is induced in rats by the daily IP administration of β,β′‐iminodipropionitrile (IDPN), 300 mg/kg, for 7 days. The levels of the biogenic amines, norepinephrine (NE), dopamine (DA), serotonin (5‐HT) and its metabolite 5‐hydroxyindoleacetic acid (5‐HIAA), were measured in the striatum, midbrian, medulla, cortex, and cerebellum on the day the syndrome appeared (day 7) and one week later (day 14). The biogenic amine most affected by IDPN administration was 5‐HT. On day 7, striatal 5‐HT level increased and 5‐HIAA levels decreased while in the medulla and midbrain, 5‐HIAA levels increased. On day 14, significant reductions in both 5‐HT, in the midbrain, striatum, and cortex, and 5‐HIAA, in all regions except the cortex, were observed. NE was markedly increased in the medulla, midbrain, and striatum on day 7, whereas on day 14 it was found to be within the normal range in these same regions. With the exception of a slight, but significant, increase in the cortex on day 7, DA levels in all regions were found to be relatively unaffected by IDPN administration on both day 7 and day 14.

In an attempt to detect degenerative changes which might be taking place in the brain and which might provide an explanation for the permanency of the behavioral disturbances, the uptake of [3H]‐labeled NE, DA, and 5‐HT into synaptosomal‐rich preparations of striatum and the uptake of NE and 5‐HT into the midbrain area were compared between normal and syndromized rats on both day 7 and day 14. Small changes were observed but they were not statistically significant.

The alterations of 5‐HT and 5‐HIAA levels in several regions of the brain under the conditions examined may indicate that IDPN's neurotoxicity primarily affects 5‐HT‐containing neurones. The active membrane transporting system of the nerve endings studied, however, remained relatively intact. This latter finding eliminates the possibility that neuronal degeneration in these areas is responsible for the decreased 5‐HT and 5‐HIAA levels or is the pathology underlying the permanency of the syndrome. These results are evaluated in terms of a possible model for hyperkinetic disorders.
Effects of catecholamines on behavior
Authors: Torda Clara
Published: January 2005

The potential for at least partial reversible transition of aggression‐ and anxiety‐type symptomatology suggested searching for a potential biochemical link between sub‐cellular mechanisms involved in the execution of aggression and anxiety. The effects of norepinephrine combined with dopamine and of epinephrine on these two types of behavior were tested. Responses to foot‐shock were used to test aggression, extinction of avoidance response was used to test anxiety‐type behavior. The results suggested that one of the possible links between the intracerebral processes responsible for execution of aggression‐ and anxiety‐type behaviors is transmethylation of norepinephrine and/or dopamine to epinephrine.
Effect of acetylcholine on the activity of dopamine β‐hydroxylase in rat brain
Authors: Karahasanoglu A. M. , Edwards E. H. , Tildon J. T. , Ozand P. T.
Published: January 2005

Sixty percent of the dopamine β‐hydroxylase (DBH) (EC 1.14.2.1) activity in rat brain was found to be bound to membrane fractions. The additions of Triton X‐100 solubilized DBH completely and permitted the estimated of the total enzyme activity. In homogenates the DBH could be detected in the absence of Triton X‐100 but was 30–45% of this total enzyme activity; in crude synaptosomal fractions this value was only 10%. Incubation of brain slices in media containing 2 × 10–3M acetylcholine (ACh) led to an increase by a factor of 2–2.5 in the activity of DBH measured in the absence of detergents; however, total enzyme activity remained the same. The addition of 6 × 10–2 M K+ in place of ACh produced a similar effect; however, the increase in the activity of DBH measured in the absence of detergents was only 25%. The effect of ACh could be reversed by removing it from the medium, or by the addition of diethyl p‐nitrophenyl phosphate (paraoxon) 4 × 10–5 M. The addition of eserine 4 × 10–4 M increased the effect of ACh at 15 min of incubation. Neither acetate nor choline had any effect. Intact cell boundaries appeared to be necessary, since addition of ACh after complete homogenization caused no increase in activity. ACh caused a (9–10)‐fold increase in the specific activity of membrane‐bound DBH but no change in the specific activity of the enzyme in cytosol. Although the effect of ACh mimicked the effect of Triton X‐100, it was not due to the solubilization of DBH. The presence of ACh did not increase the release of DBH into the incubation medium.
Changes of CTP synthetase activity during postnatal rat brain development
Authors: Genchev D. D. , Mandel P.
Published: January 2005

The activity of CTP synthetase (UTP: ammonia ligase (ADP, EC. 6.3.4.2.)) was determined in rat cerebral hemispheres and cerebellum during postnatal development. It was found that enzyme activity, when expressed per unit of protein or wet tissue weight, in both parts of the brain decreased with age, the diminution proceeding more rapidly in the cerebellum than in the hemispheres. When CTP synthetase was expressed on the basis of DNA an activity peak in the hemispheres with a maximum on the 5th day after birth was observed. The enzyme content per cell was several times lower in the cerebellum than in the hemispheres at each age studied, with the exception of 1‐day‐old animals, in which both tissues displayed intensity of RNA synthesis in the developing brain. The conclusion was reached that the changes of CTP synthetase activity were closely related to the RNA metabolism. Therefore the enzyme under study may be one of the factors involved in cell control of RNA synthesis.
Structure of neuronal assemblies in cerebral cortex
Authors: Batuev A. S. , Babmindra V. P.
Published: January 2005

Interrelations in the apical dendrite bundles of a single neuronal column were revealed by means of light and electron microscopy in the cat motor cortex. Such column presents an integrated structural module. There were also found wider joinings of several columns, among which complex coordination may exist.
Studies on the effects of chronic ethanol ingestion on the properties of rat brain ribosomes
Authors: Tewari Sujata , Murray Sandara , Noble Ernest P.
Published: January 2005

Previous observations have demonstrated decreased in vivo and in vitro protein synthesis by brain ribosomal systems following long‐term ethanol ingestion. For further investigation of the properties of brain ribosomes, the 40S and 60S ribosomal subunits were successfully isolated from control and chronic 10% ethanol‐drinking rats. For a successful dissociation of ribosomes into subunits NH4CI, puromycin and a high‐salt treatment at 10°C were essential with a critical concentration of Mg2+ since ribosomes could not be resolved at less than 7 mM Mg2+. Analysis of the A260 profile of the subunits on the sucrose gradients showed no significant differences between the control and ethanol‐ingesting groups. Studies on 3H‐labeled ribosomes following in vivo RNA labeling showed correspondence of the radioactive profiles from the incorporation of [5‐3H] orotic acid into RNA with the sucrose gradient absorbance profile of 60S and 40S ribosomal subunits. Furthermore, active reassociation of both subunits occurred at 37°C as demonstrated by the increased [14C]‐phenylalanine incorporation in the presence of poly(U). Results further showed that the poly(U)‐dependent [14C] phenylalanine incorporation was significantly reduced by the subunits from the ethanol‐ingesting animals. These findings suggest that long‐term ingestion of ethanol caused functional changes in the properties of brain ribosomes, specifically on the reassociation process of the two subunits.
Intracortical horizontal connections of neurons in cat and monkey motor cortex
Authors: Novojilova A. P. , Babmindra V. P.
Published: January 2005

The present paper deals with the study of the structure of horizontal neuron chains, one of the aspects of intracortical intraneuronal relationships. The motor cortex (field 4) of cats and lower monkeys (Papio hamadryas and Macacus rhesus s. M. Mullata) was treated by the impregnating method of Golgi‐Kopsh. The drawings of neurons from 90‐μm sections were made by means of a camera lucida.

Three possible pathways of impulse transmission along neuron chains in a horizontal direction were revealed. These were: a pyramido‐pyramidal system of connections which may possibly spread excitatory influence among several columns; a basket‐pyramidal connection system; and connections which arise from successive switchings between neighboring neurons of one layer.
Regional distribution of myelin basic protein in the central nervous system of quaking, jimpy, and normal mice during development and aging
Authors: Delassalle A. , Zalc B. , Lachapelle F. , Raoul M. , Collier P. , Jacque C.
Published: January 2005

Myelin basic protein (MBP) was quantified using a RIA technique in the spinal cord, cerebellum, diencephalon plus brainstem region and cerebral hemispheres of two dysmyelinating murine mutants, quaking (qk) and jimpy (jp) mice. Comparison was made with normal control values. The whole life‐span has been investigated: ie, ages ranging from 0 to 26 days for the jp, 0 to one year for the qk, and prenatal stage to three years for the control animals. Assays in the mutants at early ages were rendered feasible by the use of marker genes, which has allowed the diagnosis of the mutation at birth, 12 days before the expression of their typical tremor phenotype. Special care was given to the period of early myelinogenesis in order to clarify the dysynchrony between the various parts of the central nervous system.

In normal mice, MBP was already detected in the brain of 19‐day‐old embryos. During development, rapid accumulation of MBP first occurred in the spinal cord then in the diencephalon, the brainstem, the cerebellum, and finally in the cerebral hemispheres.

In the 25‐day‐old jimpy mutant, levels of MBP were found dramatically decreased, never exceeding 6% of the normal controls in any of the areas investigated.

The situation for the quaking mouse was quite different. This mutant could be investigated up to one year old. At that age, a high discrepancy was observed between the values found in the brain and in the spinal cord (respectively, 10% and 35%) compared to normal controls.

In both mutants, not only were the levels of MBP decreased, but also its appearance during development was delayed. Nevertheless, in both mutants the caudo‐rostral timing of myelination as assayed by MBP levels was maintained. Furthermore, the later myelination occurred, the stronger was the deficit in MBP. Interestingly, in the quaking mutant, the specific plasticity of the spinal cord was exemplified by its ability to reduce constantly, even at an advanced age, its initial deficit of MBP.
Laminar distribution of cholinergic markers in neocortex: Effects of lesions
Authors: Johnston M. V. , Young A. C. , Coyle J. T.
Published: January 2005

The distribution of presynaptic markers for cholinergic and GABAergic neurons in the various layers of the lateral neocortex was determined with a techique in which sections of increasing depth horizontal to the pial surface were obtained on a frozen‐stage microtome and analyzed for the markers. The specific activities of choline acetyltransferase and acetylcholinesterase had an uneven distribution in the cortex with lowest levels of activity associated with lamina II and III, whereas glutamate decarboxylase activity was highest in lamina II, III, and IV. Fetally‐induced hypoplasia of the cortex resulted in an enrichment in both choline acetyltransferase and acetylcholinesterase activity in all layers with no significant change in the activity of glutamate decarboxylase. Lesion of the nucleus basalis–cortical cholinergic pathway resulted in marked reductions in the activities of acetylcholinesterase and choline acetyltranferase in all cortical layers and an elimination of the uneven distribution of these markers within the cortex. These results provide further evidence that acetylcholinesterase activity is specifically associated with cortical cholinergic afferents and support the existence of cortical intrinsic cholinergic neurons.
Choline acetyltransferase: Further studies on the reverse reaction
Authors: Hsu Louise L. , Chao Li‐Pen
Published: January 2005

In order to further characterize the reaction mechanism of brain ChAc in its purified form, we have investigated the reverse reaction of ChAc in terms of pH optimum, salt effects, and substrate kinetics using a radiochemical assay. We directly measured the reaction product acetylcoenzyme A which was separated from the substrate ACh by a cation exchange column, Dowex 50W‐X8 (Na+ form). The reverse reaction of ChAc was linear with incubation time up to 40 minutes, and with enzyme protein concentration up to 5 μg. It had a pH optimum at 7.0. At 0.22 M the monovalent chloride and bromide salts activated the reverse ChAc activity by 23–47% but the fluoride and iodide salts inhibited the reverse enzyme activity by 10–30%. Kinetic studies in the absence of salt showed that KACh was 0.62 ± 0.06 mM, KCoA·SH was 12.68 ± 1.21 μM, and Vmax was 11.6 ± 1.0 nmol AcCoA/mg protein/min. These data are in disagreement with the values reported on partially purified ChAc from bovine brain by Glover and Potter [1971] and Hersh [1980]. This indicates that further investigations are necessary to clarify or resolve these differences.
Lipophilin‐induced experimental allergic encephalomyelitis in guinea pigs
Authors: Madrid R. E. , Wisniewski H. M. , Hashim G. A. , Moscarello M. A. , Wood D. D.
Published: January 2005

Clinical signs of EAE were infrequently observed (1/20) in adult Hartley guinea pigs challenged with isolated human myelin lipophilin in complete Freund's adjuvant. However, CNS vasculitis and parenchymal infiltration by inflammatory cells were found in 10 of 20 inoculated animals. Localized, nonconfluent, small demyelinated lesions were detected in the brain and spinal cord of 5/20 Hartley guinea pigs during an observation period of 120 days. The frequency of both inflammatory and demyelinated lesions in Hartley animals appeared to be dosedependent, but extensive demyelinated lesions were not induced. Persistent residual inoculation mixture at the site of injection was found in animals showing CNS inflammatory and/or demyelinated lesions. In contrast to the Hartley strain, young strain 13 guinea pigs were clincally and pathologically unresponsive to challenge with lipophilin and mycobacteria in water‐in‐oil emulsion.
Isoelectric focusing of the chick eye ciliary neuronotrophic factor
Authors: Manthorpe Marston , Barbin Gilles , Varon Silvio
Published: January 2005

A procedure is presented in which a crude extract from selected chick embryo intraocular tissues is submitted to analytical polyacrylamide slab gel isoelectric focusing. The extract contains a protein, ciliary neuronotrophic factor (CNTF) which can be eluted in active form from focused gels in a region occupied by only two protein bands. A “slot” technique is presented in which we demonstrate that the eluted CNTF activity focuses in the very restricted region between the two visible bands and is not associated with either band. Silver stain‐densitometry is used to correlate staining intensity with protein concentration and from such an analysis it is concluded that the CNTF protein represents an extremely low proportion of total extract protein and that the minimum CNTF specific activity eluted from gel slices is 106 trophic units per mg protein. This one‐step procedure will be used in the future to prepare highly purified CNTF for antibody generation.
Molecular requirements for survival of cultured avian and rodent dorsal root ganglionic neurons responding to different trophic factors
Authors: Skaper Stephen D. , Selak Ivan , Varon Silvio
Published: January 2005

We have previously demonstrated that both peripheral and central neurons from 8 day embryonic chick and newborn mouse can be maintained in a serum‐free medium using the N1 supplement consisting of insulin, transferrin, putrescine, progesterone, and selenite. In the present studies we show that dorsal root ganglionic (DRG) neurons from embryonic chick (E7–E15) and neonatal mouse can be cultured in a serum‐free environment with only the addition of insulin and transferrin, plus Nerve Growth Factor (NGF). Chick DRG from E10–E15 contain a population of neurons sensitive to a chick embryo eye‐derived ganglionic neuronotrophic factor (GNTF), which is distinct from the neuronal subset dependent upon NGF. The GNTF‐dependent chick neurons can also be maintained in culture with insulin and transferrin supplements. Neonatal mouse DRG neurons, whether supported by NGF or eye‐derived GNTF, likewise survive in serum‐free medium with only insulin and transferrin. Limited numbers of neurons survive for the first 24 hours in a serum‐free medium lacking insulin or transferrin, but failed to display neurite outgrowth even in the presence of added trophic factor.
Role of the plasmin‐generating system in the developing nervous tissue: I. Proteolysis as a mitogenic signal for the glial cells
Authors: Kalderon Nurit
Published: January 2005

The role of the plasmin‐generating system, a serum component, in the development of dissociated embryonic chick spinal cord cells in culture was studied. Studies were performed in a defined system where the cells were maintained in a serum‐free medium. Under these conditions the cells produce plasminogen activator. It was found that plasminogen, when added to the chemically defined culture medium at concentrations of 0.2–0.75 μg/ml, stimulates [3H]thymidine uptake (as expressed per total DNA) in a dose‐response manner. This mitogenic effect is abolished by the protease inhibitors leupeptin and aprotinin. Trypsin, but not chymotrypsin, can produce similar effects. It is concluded that plasmin, which is produced as a result of the activation of plasminogen, is a component that serves as a proliferation factor in developing spinal cords in culture.
Chicken serum transferrin duplicates the myotrophic effects of sciatin on cultured muscle cells
Authors: Oh Tae H. , Markelonis George J.
Published: January 2005

Sciatin, a glycoprotein purified from chicken sciatic nerves, has been shown to have trophic effects on chicken skeletal muscle cells in culture. Since we recently observed pronounced structural similarities between sciatin and chicken serum transferrin [Markelonis et al, 1982a], we decided to investigate the muscle growth‐promoting activity of transferrin on cultured muscle cells. Serum transferrin was isolated by the same protocol used to purify sciatin, viz., affinity chromatography on concanavalin Aagarose followed by ion‐exchange chromatography on DEAE cellulose. The serum protein recovered by this purification scheme was indistinguishable immunologically from sciatin as evidenced by a positive precipitin reaction against goat anti‐sciatin serum on double immunodiffusion in agar. Purified serum transferrin had myotrophic effects identical to those of sciatin when added to skeletal muscle cells in vitro. For example, even when chicken embryo extract—a constituent normally required for chicken muscle cell differentiation in vitro—was omitted from culture medium, either serum transferrin or sciatin promoted myogenesis in culture as measured by a stimulation of the fusion index. Furthermore, both proteins caused a significant increase in the level of protein synthesis, the number of acetylcholine receptors and the activity of acetylcholinesterase in treated muscle cultures. By contrast, commercially obtained ovotransferrin (conalbumin) or FeSO4 (100 μM) were unable to fully support myogenesis of skeletal muscle in vitro if embryo extract was omitted from the culture medium. From these data, we conclude that the neuronal myotrophic protein sciatin is both structurally and biologically related to serum transferrin. Furthermore, we suggest that sciatin may represent a neuronal form of this iron‐transport protein.
Dose‐dependent initiation of myogenesis by neurotrophic factor
Authors: Popiela Heinz , Ellis Stanley , Festoff Barry W.
Published: January 2005

The kinetics of primary chick muscle cells in response to partially purified neurotrophic factor (NTF) were investigated. Chick muscle cells are routinely plated in the absence of NTF but in the presence of horse serum to allow cell attachment to the substratum; a maximum number of cells attaches 5–8 hr after plating, but cells do not proliferate in the absence of NTF, or do so extremely slowly. Subsequent to a routine attachment period of 6 hr, the medium is aspirated and replaced with medium containing 2–20 μg/ml of NTF as well as horse serum. Dose responsiveness at elevated NTF concentrations is observed only if F12 medium, supplemented with serum, insulin, transferrin, and selenium is used. In the presence of commercial F10, although supplemented with serum, dose responsiveness is not apparent at more than 2 μg/ml of NTF. Upon exposure to NTF, in the presence of supplemented F12 and serum, an 8‐hr lag ensues; then, thymidine is incorporated at NTF dose‐dependent rates by growing cell populations. The rates of incorporation into cell populations depend on the initial number of cells plated and the amount of NTF supplied. Cell counting indicates that dose‐dependent proliferation of muscle cells has occurred during the first 48 hr of exposure to NTF. The specific activity of NTF is repeatedly shown to be at least 10‐fold greater than unfractionated nerve extract. Shortly after 48 hr of exposure to NTF, myoblasts characteristically begin to fuse with one another, and myogenesis is visible. These studies show that the initiation of in vitro myogenesis in primary chick muscle cells depends on the amount of NTF supplied. The work also indicates a requirement for optimum medium conditions in order to detect dose–responses to NTF.
Acute and chronic effects of antidepressant drugs on β‐adrenergic function in astrocytes in primary cultures: An indication of glial involvement in affective disorders?
Authors: Hertz L. , Richardson J. S.
Published: January 2005

Acute and chronic effects of the antidepressant drugs tranylcypromine, a monoamine oxidase inhibitor, and amitriptyline, a monoamine uptake inhibitor, were studied on β‐adrenergic receptor function in mouse astrocytes in primary cultures. In clinically relevant concentrations, acute administration of either antidepressant drug had a direct inhibitory effect on the binding of the β‐adrenergic ligand dihydroalprenolol and on the isoproterenol‐induced accumulation of cyclic AMP. However, in the absence of isoproterenol, these drugs enhanced the formation of cyclic AMP in the astrocytes. Chronic exposure to amitriptyline or tranylcypromine led to a decrease in isoproterenol‐induced accumulation of cyclic AMP, and the time course for the development of this phenomenon was similar to that reported for whole brain in vivo. These findings suggest that these antidepressant drugs act as partial agonists at β‐adrenergic receptors on astrocytes, and that the down‐regulation of β‐adrenergic activity that occurs in vivo after chronic administration of antidepressant drugs may, to a large extent, take place in astrocytes and may result from the partial /3‐agonist nature of the drugs.
Serum‐ and substratum‐dependent modulation of neuritic growth
Authors: Skaper Stephen D. , Selak I. , Varon S.
Published: January 2005

Explants of embryonic day 8 (E8) chicken dorsal root ganglia (DRG) have been cultured with medium containing serum or the serum‐free supplement N1 on one of three substrata: collagen, polyornithine (PORN), or PORN exposed to a polyornithine‐binding neurite‐promoting factor (PNPF‐PORN). Replicate cultures were maintained with or without nerve growth factor (NGF). NGF elicited its classical neuritic outgrowth on all three substrata in serum‐containing or serum‐free medium. In the absence of NGF, however, a gradation of increasing neurite growth was seen with: PNPF‐PORN > PORN > collagen. This response occurred in both media. In addition, the neuritic halo in each instance was markedly more developed in the absence of serum, especially on PNPF‐PORN. Nonneuronal behaviors reflected both serum and substratum influences: thus, nonneuronal outgrowth consisted mainly of flat cells with serum and collagen, was nonexistent with serum and PORN or PNPF‐PORN, and involved mostly Schwann‐like scattered cells in the absence of serum on any one substratum. The serum‐dependent behaviors of ganglionic neurites were examined further with explants from chicken E11 sympathetic ganglia. A single substratum was used (PORN), without exogenous trophic factor. Neurite outgrowth was depressed by the presence of fetal calf serum, thus supportig the generality of this phenomenon. Lastly, PC12 cells, a clonal line of rat pheochromocytoma, will grow neurites in the presence of NGF after 48 hr in serum‐free, but not serum‐containing media. Addition of serum to serum‐free cultures at this time results in the rapid and complete retraction of neurites.
Enzyme changes in axon, myelin, and Schwann cells in injured sciatic nerve
Authors: Lapin Evelyn P. , Weissbarth S. , Maker H. S. , Lehrer G. M. , Weiss C.
Published: January 2005

Four enzymes related to specific cell functions were assayed in rat sciatic nerve injury by crush (cr) or crush and ligation (cr‐lig) after 2, 7, and 15 days in situ. Enzyme activities in segments of sciatic nerve proximal and distal to the injury were compared to those in corresponding segments of the contralateral nerve. Choline acetyltransferase (CAT) activity in the distal portion decreased by 65% for cr and almost to zero for cr‐lig by day 7, while in the proximal portions CAT decreased to 70% of control values by 7 days and to 50% at 15 days after cr‐lig.

The activity of the Schwann cell–myelin‐associated enzyme 2′,3′‐cyclic nucleotide phosphohydrolase (CNP) decreased slowly distal to the injury. Distal to both types of injury the lysosomal enzyme beta‐glucuronidase (GLR) increased six‐ to eightfold by 15 days. Proximal to injury GLR also increased (P cr × 2.5, P cr‐lig × 5) but the peak proximally was attained by day 7. Despite interruption of axonally transported enzymes, the activities of the metabolic enzyme creatine kinase (CK) increased distal to injury apparently reflecting changes in the functions of the Schwann cells. The loss of metabolic enzymes from the axonal compartment may be completely obscured by reciprocal changes in the nonneuronal compartments if the activity is present in both compartments.
Regional cell count and respiration in the brain of Rana catesbeiana
Authors: Yeaman R. R. , Potter Richard L.
Published: January 2005

Cell counts were made in three divisions of the bullfrog brain: (1) olfactory lobes‐telencephalon, (2) diencephalon‐mesencephalon, and (3) the hindbrain; average cellular respiration in potassium‐enriched Ringer solution and the rate of respiration in sodium‐free medium were tested for their possible relationship to the numbers of glia and numbers of neurons in each region. After restoring some of the sodium ions to sodium‐free minces, the percent increase in respiration was plotted for each brain segment and compared to the percent of glia per brain division to determine the glial respiratory contribution. Where glial numbers were greater, the potassium‐stimulated respiration was greater; where neuronal numbers were greater, the sodium‐free respiration was most prominent. The respiration increased most above the sodium‐free rate, when sodium ions were added or when the full amount of sodium was present, in the hindbrain, where the glia appear to metabolize more vigorously and the neurons least actively.
Glycoprotein properties of benzodiazepine receptors from calf cerebral cortex
Authors: Sherman‐Gold Rivka , Dudai Y.
Published: January 2005

Several lectins (concanavalin A, wheat germ agglutinin, wax bean agglutinin, and phytohemagglutinin) induce aggregation and precipitation of deoxycholate‐solubilized benzodiazepine receptors from calf cerebral cortex. These receptors were also retained on columns of immobilized lectins. Photoaffinity labeling of the soluble benzodiazephine receptors prevented their interaction with lectins. Periodate treatment caused inactivation of benzodiazepine receptors which was partially prevented by diazepam and/or γ‐aminobutyric acid. The possible association of the drug‐binding site and the carbohydrate moiety is discussed.
Apparent turnover of norepinephrine in the intact rat brain estimated from its rate of appearance in the cerebroventricular compartment
Authors: Levitt Morton , Kowalik S. , Barkai A. I.
Published: January 2005

The apparent turnover of norepinephrine (NE) in the intact brain of urethane‐anesthetized rats was estimated in vivo from the rate of appearance of endogenous NE in the cerebroventricular compartment. Ventriculocibternal perfusion, a radioenzymatic assay for endogenous NE and isotope dilution of 3H‐NE were used to determine the rate of appearance (Ra) of NE. The effect of tranylcypromine, a monoainine oxidase (MAO) inhibitor and releasing agent on Ra of NE, was also studied. In control animals, the mean Ra value was 0.40 pmol/min. Pretreatment with tranylcypromine resulted in a threefold increase in the mean value for Ra, which was due to increased secretion of NE into the CSF. The results indicate that 90% of the NE entering the cerehroventricular compartment was removed. Pretreatment with tranylcypromine did not modify removal, thus suggesting that tranylcypromine has no effect on the physiological processes which regulate the removal of NE from the CSF.
Effects of excitatory amino acids, and of their agonists and antagonists on the release of neurotransmitters from the chick retina
Authors: Morán J. , Pasantes‐Morales H.
Published: January 2005

Effects of glutamic, aspartic, and cysteic acid, and of kainic acid and N‐methyl aspartate on the release of labeled GABA, glycine, and taurine were examined in isolated, perfused chick retina. Glutamic acid (0.5‐2 mM), increased the release of 3H‐GABA by more than four times and that of 14C‐glycine by about two times. The release of GABA decreased 50% and that of glycine 95% in the presence of the antagonist of glutamic acid receptors, glutamate diethyl ester (300 m̈M). N‐methyl aspartate, used as an agonist of aspartic acid receptors, preferentially increased the release of GABA (seven times) over that of glycine (three times). The stimulatory effect of N‐methyl aspartate was antagonized by D‐α aminoadipate and by Mg. Kainic acid (10 m̈M) induced the release of glycine but not that of GABA. Cysteic acid failed to modify the release of any of the amino acids examined. The efflux of labeled taurine was practically unaffected by all the compounds utilized. The release of GABA by the excitatory amino acids and agonists was Ca‐independent but Na‐dependent, whereas the release of glycine was markedly Ca‐dependent. The evidence presented here suggests that experimental conditions activating receptors of excitatory amino acids differently affect the release of inhibitory amino acids.
Learning deficits on avoidance task and hippocampal lesions in area CA3 following intraperitoneal administration of 3‐acetylpyridine
Authors: Ozaki H. S. , Murakami T. H. , Shimada M.
Published: January 2005

Young adult mice of the ddN‐F26 strain were given a single intraperitoneal injection of 3‐acetylpyridine (3‐AP) at a dosage of 200 mg/kg body weight. Two weeks after this treatment, learning on avoidance task was tested with a training apparatus called a jump‐box. Each mouse was subjected to 30 trials of training per week for 3 or 4 weeks.

Contrasted to untreated mice, the mean performance of the 3‐AP‐treated mice on avoidance training was significantly reduced in every weekly training session. However, since the learning scores of individual 3‐AP‐treated mice were highly varied, these mice were divided into several groups according to the characteristics of their learning patterns in order to analyze the relationships between learning ability and brain damage. It was found that there was a close association between the rate of learning deficits and the degree of destruction of the pyramidal cells in area CA3 of the hippocampus in mice treated with 3‐AP. The present data suggest that the area CA3 neurons play an important role on the acquisition of avoidance task and memory formation.