bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphoethanolamine Enhances High‐Affinity Choline Uptake and Acetylcholine Synthesis in Dissociated Cell Cultures of the Rat Septal Nucleus
Authors: Bostwick J. Robert , Abbe Russell , Appel Stanley H. 
Published: October 2006

AbstractDissociated rat septal nucleus cells cultured in defined medium exhibited twofold increases in the maximal rates of sodium‐dependent, high‐affinity choline uptake and acetylcholine formation when grown in the presence of phosphoethanolamine. The effect was concentration‐dependent (EC50= 15 μM) and appeared to be associated with in vitro maturation of cholinergic neurons rather than with enhanced survival. Choline acetyltransferase, acetylcholin‐esterase, and choline kinase activities were unaffected by this treatment. The effect of phosphoethanolamine was specific for cholinergic neurons, because treatment with this compound did not alter the kinetic constants for high‐affinity neuronal uptake of γ‐aminobutyric acid or dopamine. The action appeared to be mediated primarily through activation of the sodium‐dependent, high‐affinity transport mechanism for choline as opposed to alterations in the storage and release of acetylcholine.
Metabotropic Glutamate Receptor Activation Produces Extrapyramidal Motor System Activation That Is Mediated by Striatal Dopamine
Authors: Sacaan Aida I. , Bymaster Frank P. , Schoepp Darryle D. 
Published: October 2006

AbstractLittle is known about the in vivo function of the GTP‐binding protein‐coupled “metabotropic” excitatory amino acid (EAA) receptor. In vitro studies on agonist‐induced brain phosphoinositide hydrolysis have shown that (15,3i?)‐1‐aminocyclopentane‐l,3‐dicarboxylic acid is a highly selective and efficacious metabotropic EAA agonist. We have recently reported that in vivo unilateral intrastria‐tal injection of (15′,3.K)‐l‐aminocyclopentane‐l,3‐dicar‐boxylic acid induces transient extrapyramidal motor activation that manifests itself as contralateral turning. In this study, we fully characterized the onset of turning behavior following intrastriatal (1S,3.R)‐1‐aminocyclopentane‐l,3‐dicarboxylic acid injection and the possible involvement of striatal dopamine neurons in the mediation of this effect. Rats were anesthetized with the short‐acting agent halo‐thane to allow for rapid surgical recovery and thus early behavioral measurements. Intrastriatal (1S,3R)‐1‐aminocy‐clopentane‐l,3‐dicarboxylic acid (1 μmol/2 μl) produced an incremental increase in contralateral turning starting at 1 h and plateauing 3–6 h after injection (peak effect, 39.1 ± 6.7 rotations per 5 min). Dopamine depletion with α‐methyl‐DL‐p‐tyrosine (250 mg/kg i.p., 80% depletion) resulted in >85% inhibition of (1S,3R)‐1‐aminocyclopentane‐l,3‐di‐carboxylic acid‐induced contralateral turning. The dopamine antagonist haloperidol (0.3 mg/kg i.p.) produced 48% inhibition of the (1S,3R)‐1‐aminocyclopentane‐1,3‐dicar‐boxylic acid response. In time course studies, turning behavior correlated with increases in levels of the dopamine metabolites 3,4‐dihydroxyphenylacetic acid and homovanillic acid. These results suggest a functional interaction between the metabotropic EAA receptor and the dopami‐nergic system in the striatum.
Differences in Dopamine Clearance and Diffusion in Rat Striatum and Nucleus Accumbens Following Systemic Cocaine Administration
Authors: Cass Wayne A. , Gerhardt Greg A. , Mayfield R. Dayne , Curella Pamela , Zahniser Nancy R. 
Published: October 2006

AbstractAcute cocaine administration preferentially increases extracellular dopamine levels in nucleus accumbens as compared with striatum. To investigate whether a differential effect of cocaine on dopamine uptake could explain this observation, we used in vivo electrochemical recordings in anesthetized rats in conjunction with a paradigm that measures dopamine clearance and diffusion without the confounding effects of release. When a finite amount of dopamine was pressure‐ejected at 5‐min intervals from a micropipette adjacent to the electrode, transient and reproducible increases in dopamine levels were detected. In response to 15 mg/kg of cocaine‐HCl (i.p.), these signals increased in nucleus accumbens, indicating significant inhibition of the dopamine transporter. The time course of the dopamine signal increase paralleled that of behavioral changes in unanesthetized rats receiving the same dose of cocaine. In contrast, no change in the dopamine signal was detected in dorsal striatum; however, when the dose of cocaine was increased to 20 mg/kg, enhancement of the dopamine signal occurred in both brain areas. Quantitative auto‐radiography with [3H]mazindol revealed that the affinity of the dopamine transporter for cocaine was similar in both brain areas but that the density of [3H]mazindol binding sites in nucleus accumbens was 60% lower than in dorsal striatum. Tissue dopamine levels in nucleus accumbens were 44% lower. Our results suggest that a difference in dopamine uptake may explain the greater sensitivity of nucleus accumbens to cocaine as compared with dorsal striatum. Furthermore, this difference may be due to fewer dopamine transporter molecules in nucleus accumbens for cocaine to inhibit, rather than to a higher affinity of the transporter for cocaine.
Somatostatin Content Increases Following Norepinephrine Depletion in Frontal Cortex of l‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine‐Treated Mice
Authors: Mitsuo Kunihiko , Schwartz Joan P. 
Published: October 2006

AbstractThe effects of l‐methyl‐4‐phenyl‐l,2,3,6‐tetrahy‐dropyridine (MPTP) on somatostatin (SS)‐containing neurons were examined by measuring dopamine, norepinephrine (NE), SS, and SS mRNA in striatum and frontal cortex of C57/B16 mice at various times following treatment with MPTP‐HC1 (96 mg/kg i.p.). MPTP caused a 70% depletion of dopamine in striatum by 1 day and a 40% depletion of NE in frontal cortex within 3 days. SS content was increased in frontal cortex 4 days later, but not in striatum; there were no changes in SS mRNA. Maprotiline, a specific NE‐uptake blocker, prevented both the depletion of NE and the increase of SS in frontal cortex due to MPTP administration. These results support the possibility that NE can regulate SS in frontal cortex and are discussed in terms of the decrease of SS seen in parkinsonian patients with dementia.
Pharmacological Characterization and Autoradiographic Localization of Histamine H2 Receptors in Human Brain Identified with [125I]Iodoaminopotentidine
Authors: Traiffort E. , Pollard H. , Moreau J. , Ruat M. , Schwartz J. C. , Martinez‐Mir M. I. , Palacios J. M. 
Published: October 2006

Abstract 125I‐Aminopotentidine (125I‐APT), a reversible probe of high specific radioactivity and high affinity and selectivity for the H2 receptor, was used to characterize and localize this histamine receptor subtype in human brain samples obtained at autopsy. On membranes of human caudate nucleus, specific 125I‐APT binding at equilibrium revealed a single component, with a dissociation constant of 0.3 nM and maximal capacity of about 100 fmol/mg of protein. At 0.2 nM, 125I‐APT specific binding, as defined with tiotidine, an H2‐receptor antagonist chemically unrelated to iodoaminopotentidine, represented 40–50% of the total. Specific 125I‐APT binding was inhibited by a series of typical H2‐receptor antagonists that displayed apparent dissociation constants closely similar to corresponding values at the reference biological system, i.e., guinea pig atrium. This indicates that the pharmacology of the H2 receptor is the same in the human brain as on this reference system. However, histamine was about 10‐fold more potent in inhibiting 125I‐APT binding to membranes of human brain than of guinea pig brain. 125I‐APT binding was also inhibited by amitriptyline and mianserin, two antidepressant drugs, in micromolar concentrations corresponding to effective plasma concentrations of treated patients. The distribution of H2 receptors was established autoradiographically with 125I‐APT on a series of coronal sections of human brain after assessing the pharmacological specificity of the labeling. The highest density of 125I‐APT sites was found in the basal ganglia, various parts of the limbic system, e.g., hippocampus or amygdaloid complex, and the cerebral cortex. H2 receptors displayed a laminar distribution in cerebral cortex and hippocampal formation. A low density of sites was found in cerebellum as well as in hypothalamus, the brain area where all the perikarya and the largest number of axons of histaminergic neurons are found. The widespread distribution of H2 receptors in the human brain is consistent with the alleged modulatory role of histamine mediated by this subtype of receptor.
Cell Swelling, Blebbing, and Death Are Dependent on ATP Depletion and Independent of Calcium During Chemical Hypoxia in a Glial Cell Line (ROC‐1)
Authors: Jurkowitz‐Alexander Marianne S. , Altschuld Ruth A. , Hohl Charlene M. , Johnson J. David , McDonald John S. , Simmons Todd D. , Horrocks Lloyd A. 
Published: October 2006

AbstractThe morphological and biochemical changes that occur during chemical hypoxic injury in a neural cell line were studied in the presence and absence of calcium. Oligo‐dendroglial‐glioma hybrid cells (ROC‐1) were subjected to inhibitors of glycolytic and oxidative ATP synthesis (chemical hypoxia). Complete respiratory inhibition depleted [ATP] to <5% of control by 4 min. Blebs appeared on the cell surfaces and cells began to swell within a few minutes of ATP depletion. A 200% increase in cell volume and bleb coalescence preceded irreversible cell injury (lactate dehy‐drogenase release) which began at ∼20 min with 50% cell death by 40 min. In energized cells an equivalent degree of osmotic swelling induced by ouabain inhibition of the Na+, K+‐ATPase pump did not produce blebbing or cell death. Partial inhibition of respiration decreased [ATP] to ∼10% of control by 40 min. Blebbing and swelling began at 40 min and bleb coalescence preceded plasma membrane disruption which began at ∼55 min. ATP depletion, blebbing, swelling, and death followed similar time courses in the presence or absence of extracellular calcium ([Ca2+]e). Intracel‐lular calcium ([Ca2+]i) was measured using fura‐2. In calcium‐containing medium metabolic inhibition caused a transient increase in resting [Ca2+]i (100 ± 17 nM) followed by a low steady‐state level preceding plasma membrane disruption. Following deenergization in calcium‐free medium, [Ca2+]i remained below 60 nM throughout injury and death. These data suggest that decreased ATP initiates a sequence of events including bleb formation and cell swelling that lead to irreversible cell injury in the absence of large increases in [Ca2+]i.
Brain α‐Ketoglutarate Dehydrotenase Complex Activity in Alzheimer's Disease
Authors: Mastrogiacomo Frank , Bergeron Catherine , Kish Stephen J. 
Published: October 2006

AbstractWe measured the activity of the a‐ketoglutarate dehydrogenase complex (α‐KGDHC), a rate‐limiting Krebs cycle enzyme, in postmortem brain samples from 38 controls and 30 neuropathologically confirmed Alzheimer's disease (AD) cases, in both the presence and absence of thiamine pyrophosphate (TPP), the enzyme's cofactor. Statistically significant correlations between brain pH and lactate levels and α‐KGDHC activity in the controls were observed, suggesting an influence of agonal status on the activity of α‐KGDHC. As compared with the controls, mean α‐KGDHC activity, with added TPP, was significantly (p < 0.005) reduced in AD brain in frontal (‐56%), temporal (‐60%), and parietal (‐68%) cortices, with the reductions (‐25 to ‐53%) in the occipital cortex, hippocampus, amygdala, and caudate failing to reach statistical significance. In the absence of exogenously administered TPP, mean a‐KGDHC activity was reduced to a slightly greater extent in all seven AD brain areas (‐39 to ‐83%), with the reductions now reaching statistical significance in the four cerebral cortical areas and hippocampus. A statistically significant negative correlation was observed between α‐KGDHC activity and neurofibrillary tangle count in AD parietal cortex, the brain area exhibiting the most marked reduction in enzyme activity; this suggests that the enzyme activity reduction in AD brain may be related to the disease process and severity. In each brain area examined, TPP produced a greater stimulatory effect on α‐KGDHC activity in the AD group (23–280% mean stimulation) as compared with the controls (‐4 to ±50%); this TPP effect could be explained by reduced endogenous TPP levels in AD brain. Reduced brain α‐KGDHC activity could be consequent to loss of neurons preferentially enriched in α‐KGDHC, a premortem reduction in TPP levels (which may have affected enzyme stability), elevated brain levels of the α‐KGDHC inhibitor ammonia, or an actual failure in the expression of the gene encoding the enzyme. We suggest that a defect in this key Krebs cycle enzyme could contribute to an impairment of cerebral energy metabolism and the brain dysfunction in AD.
Expression of Facilitative Glucose Transporter Isoforms in Human Brain Tumors
Authors: Nagamatsu Shinya , Sawa Hiroki , Wakizaka Akira , Hoshino Takao 
Published: October 2006

AbstractThe expression of facilitative glucose transporter (GLUT) isoforms in human astrocytic tumors was examined. Reverse transcriptase‐polymerase chain reaction of a surgically biopsied glioblastoma was carried out using the degenerative oligonucleotide primers corresponding to the sequences of the human facilitative glucose transporter family, and polymerase chain reaction products were hybridized with human GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5 cDNA probes. The results showed that a biopsied glioblastoma expressed GLUT1, GLUT3, and GLUT4 glucose transporter genes. Northern blot analysis of total RNA (10 μg) from a biopsied glioblastoma showed the transcripts of only GLUT1 and GLUT3, suggesting that the expression of insulin‐responsive glucose transporter GLUT4 mRNA is relatively low. Immunoblot analysis of biopsied glioblastoma tissues by polyclonal antibodies against the C‐terminal synthetic peptides of GLUT1, GLUT3, and GLUT4 showed a single band of each polypeptide. However, elevated expression of GLUT1 and GLUT3 glucose transporters was not observed in the glioblastoma. Astrocytic tumor tissues (n = 14) were also examined immunohistochemically. Reactive products for GLUT1 were observed in the luminal surface of capillaries in all cases, whereas tumor cells were positive for GLUT1 in only two of 14 cases. GLUT3 was positive in astrocytic tumor cells in all cases. Three of 14 cases expressed the GLUT4 protein, which was localized in the cytoplasm of tumor cells. These results suggest that the facilitative glucose transport may be altered in astrocytic tumor cells and thus display a significant change in glucose metabolism.
Kynurenine Pathway Enzymes in Brain: Responses to Ischemic Brain Injury Versus Systemic Immune Activation
Authors: Saito Kuniaki , Nowak Thaddeus S. , Suyama Kazuhiko , Quearry Bonnie J. , Saito Misato , Crowley Jeffrey S. , Markey Sanford P. , Heyes Melvyn P. 
Published: October 2006

AbstractAccumulation of l‐kynurenine and quinolinic acid (QUIN) in the brain occurs after either ischemic brain injury or after systemic administration of pokeweed mitogen. Although conversion of l‐[13C6]tryptophan to [13C6]‐QUIN has not been demonstrated in brain either from normal gerbils or from gerbils given pokeweed mitogen, direct conversion in brain tissue does occur 4 days after transient cerebral ischemia. Increased activities of enzymes distal to indoleamine‐2,3‐dioxygenase may determine whether l‐kynurenine is converted to QUIN. One day after 10 min of cerebral ischemia, the activities of kynureninase and 3‐hydroxy‐3,4‐dioxygenase were increased in the hippocampus, but local QUIN levels and the activities of the indoleamine‐2,3‐dioxygenase and kynurenine‐3‐hydroxylase were unchanged. By days 2 and 4 after ischemia, however, the activities of all of these enzymes in the hippocampus as well as QUIN levels were significantly increased. Kynurenine aminotransferase activity in the hippocampus was unchanged on days 1 and 2 after ischemia but was decreased on day 4, at a time when local kynurenic acid levels were unchanged. A putative precursor of QUIN, [13C6]anthranilic acid, was not converted to [13C6]‐QUIN in the hippocampus of either normal or 4‐day postischemic gerbils. Gerbil macrophages stimulated by endo‐toxin in vitro converted l‐[13C6]tryptophan to [13Ce]QUIN. Kinetic analysis of kynurenine‐3‐hydroxylase activity in the cerebral cortex of postischemic gerbils showed that Vmax increased, without changes in Km. Systemic administration of pokeweed mitogen increased indoleamine‐2,3‐dioxygenase and kynureninase activities in the brain without significant changes in kynurenine‐3‐hydroxylase or 3‐hydroxyanthranilate‐3,4‐dioxygenase activities. Increases in kynurenine‐3‐hydroxylase activity, in conjunction with induction of indoleamine‐2,3‐dioxygenase, kynureninase, and 3‐hydroxyanthranilate‐3,4‐dioxygenase in macro‐phage infiltrates at the site of brain injury, may explain the ability of postischemic hippocampus to convert l‐[13C6]tryptophan to [13C6]QUIN.
Interconvertible Kinetic States of t‐Butylbicycloorthobenzoate Binding Sites of the γ‐Aminobutyric AcidA Ionophores
Authors: Maksay Gabor , Van Rijn Clementina M. 
Published: October 2006

AbstractThe kinetics of t‐[3H]butylbicycloorthobenzoate (TBOB) binding to the convulsant sites of the γ‐aminobutyric acidA (GABAA) receptor‐ionophore complex were examined in synaptosomal membrane preparations of rat brain. On and off rates of TBOB binding were accelerated by 1 μM GABA and decelerated by 1 μM bicuculline methochloride, a GABAA antagonist. The presence of GABA and bicuculline methochloride created rapid and slow phases of dissociation, respectively. The three groups of rate constants distinguished for the dissociation of 4 nM and 30 nM [3H]TBOB represent multiaffinity states of the convulsant sites depending on the presence of GABA or bicuculline methochloride. Apparent association rate constants do not obey the equation kapp=koff±kon [TBOB] without assuming interconvertibility of the kinetic states during binding. Avermectin B1a (AVM B1a), a chloride channel opening agent, accelerated the association and dissociation of TBOB and resulted in a biphasic effect on TBOB binding, i.e., enhancement at low concentrations (EC50, 7.8 nM) followed by displacement at high concentrations (IC50 6.3 μM) of AVM B1a. AVM B1a resulted in similar biphasic effects on t‐ [35S]butylbicyclophosphorothionate binding. DIDS, an isothiocyanatostilbene derivative with irreversible anion channel blocking effect, selectively inhibited basal [3H]TBOB binding (IC50 125 μM DIDS) leaving the enhancement by AVM B1a unaffected.
Soluble and Particulate Organophosphorus Neuropathy Target Esterase in Brain and Sciatic Nerve of the Hen, Cat, Rat, and Chick
Authors: Tormo Nieves , Gimeno Juan Ramón , Sogorb Miguel Angel , Díaz‐Alejo Nuria , Vilanova Eugenic 
Published: October 2006

AbstractConsiderable evidence exists suggesting that the so‐called neuropathy target esterase (NTE) is involved in the mechanisms responsible for organophosphorus‐induced delayed polyneuropathy (OPIDP). Earlier studies in the adult hen, the habitually employed experimental model in OPIDP, have shown that most NTE activity in the brain is centered in paniculate fractions, whereas approximately 50% of this activity in the sciatic nerve is encountered in soluble form, with the rest being paniculate NTE. In the present work, we have studied the paniculate and soluble fractional distribution of paraoxon‐resistant phenylvalerate esterase activity (B activity), parabxon‐ and mipafox‐resistant phenylvalerate esterase activity (C activity), and NTE activity (B ‐ C) according to ultracentrifugation criteria (100,000 g for 1 h). To this effect, two sensitive (adult hen and cat) and two scarcely sensitive (rat and chick) models were used. In all four experimental models, the distribution pattern was qualitatively similar: B activity and total NTE were much greater in brain (900–2, 300 nmol/min/g of tissue) than in sciatic nerve (50–100 nmol/min/g of tissue). The proportion of soluble NTE in brain was very low (<2%), whereas its presence in sciatic nerve was substantial (30–50%). The NTE/B ratio in brain was high for the particulate fraction (>60%) and low in the soluble fraction (7–30%); in sciatic nerve the ratio was about 50% in both fractions. Slight quantitative differences were observed in terms of OPIDP sensitivity: the proportion of soluble NTE in sciatic nerve was slightly higher in the sensitive animals (hen and cat: 49 and 44%, respectively) than in the rat and chick (41 and 37%, respectively), although no differences were noted in terms of concentration (in nanomoles per minute per gram of tissue). It is concluded that the distribution pattern of the activities studied is similar in all four experimental models, with no important quantitative differences directly related to species sensitivity or age.
Decline in Response to Nicotine in Aged Rat Striatum: Correlation with a Decrease in a Subpopulation of Nicotinic Receptors
Authors: Schulz David W. , Kuchel George A. , Zigmond Richard E. 
Published: October 2006

AbstractSpecific and reproducible changes involving the cholinergic and dopaminergic systems have been described in both the aging rodent and the human nervous system. Nevertheless, relatively little information is available on changes in nicotinic cholinergic receptors occurring in normal aging, and there have been few attempts to correlate alterations in receptor densities with changes in nicotinic actions. We have utilized the nicotine‐mediated stimulation of endogenous dopamine efflux in a striatal slice preparation as a functional index of responsiveness to nicotine in aging. Following incubation with nicotine, this efflux was significantly lower in 25‐month‐old (aged) as opposed to 4‐month‐old (young) rats. In contrast, the release of striatal dopamine following a high‐potassium stimulus was similar at both ages. Binding studies in young and aged animals did not reveal any significant change with age in the total number of striatal nicotinic receptors recognized by either [3H]nicotine or the neuronal nicotinic antagonist 125l‐neuronal bungarotoxin. However, there was a nearly 80% decline in the subpopulation of striatal nicotinic receptors jointly recognized by both nicotine and neuronal bungarotoxin, but not by α‐bungarotoxin. Quantitative autoradiography demonstrated declines with age in this receptor subtype in several brain regions examined. Decrements in this specific subpopulation of nicotinic receptors or in the nerve cells expressing these receptors may contribute to the functional declines that take place in the aging motor and visual systems.