Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.15 (glutamate decarboxylase)
 2,169 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential neuroprotective effects of IL-6 against the excitotoxic neuronal loss induced by N-methyl-D-aspartate (NMDA) have been studied. Infusion into the rat striatum of excitotoxic amounts (250 nmol) of NMDA resulted in a 45% decrease in striatal choline acetyl transferase activity (ChAT; a marker of cholinergic neurons) and glutamate decarboxylase (GAD, a marker of GABAergic neurons) at 2 days post-injection. Co-infusion of 10 U of IL-6 reduced the loss of ChAT activity to 21% but failed to prevent the loss of GAD activity. IL-6 per se, up to the dose of 500 U, failed to affect ChAT or GAD activities. The in vivo effects of IL-6 are not mediated by a direct antagonism of NMDA toxicity, since IL-6 (up to a concentration of 500 and 5000 U/ml, respectively) did not antagonize either the increase in cyclic GMP levels resulting from NMDA receptor activation in cerebellar slices or the glutamate-induced release of lactate dehydrogenase, an index of neurotoxicity, by cultured cortical neurons. These results suggest that the increase in IL-6 levels observed in experimental brain lesions may play a role in the protection and regeneration of cholinergic neurons.
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PMID:Local infusion of interleukin-6 attenuates the neurotoxic effects of NMDA on rat striatal cholinergic neurons. 133 14

The striatum of adult rats was bilaterally lesioned with stereotaxic injections of ibotenic acid in a dose (16 nmoles) that resulted in subtotal lesions. Some rats received systemic ganglioside treatment starting the day before operation and lasting for 6 or 24 days after operation; they were compared with lesioned rat receiving systemic saline injections as well as with corresponding groups of sham-operated animals. Specific neurochemical markers for cholinergic neurons (choline acetyltransferase, ChAT), GABAergic neurons (glutamate decarboxylase; GAD), and astrocytes (glutamine synthetase; GS) were assayed to asses the neurochemical recovery promoted by ganglioside treatment. Twenty-four, but not six, days after operation a significant increase of ChAT and GAD was measured in the striatum of lesioned rats treated with gangliosides in comparison with the saline group. Furthermore, a significant increase of both enzymes occurred in the striatum of lesioned rats receiving ganglioside treatment for 24 days in comparison with rats receiving ganglioside treatment for 6 days only. A small but significant increase of ChAT was measured in the striatum of sham-operated rats after 24 days of ganglioside treatment in comparison with the corresponding saline group. Finally, the increase of GS caused by the glial reaction to the ibotenic acid lesion was not affected by ganglioside treatment. The results indicate that a relatively long-lasting ganglioside treatment stimulates the recovery of specific neuronal transmitter markers and that some effect is, in addition, exerted on unlesioned cholinergic striatal neurons.
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PMID:Effects of short- and long-term ganglioside treatment on the recovery of neurochemical markers in the ibotenic acid-lesioned rat striatum. 197 26

An antiserum to choline acetyltransferase, partially purified from bovine brain (anti-ChAT 1), when incubated with synaptosomes prepared from rat cerebral cortex in the presence of complement caused release of 10% of lactate dehydrogenase and 27% of ChAT. Sodium-dependent uptake of choline was totally abolished. Similar results were obtained when an antiserum to ChAT highly purified from pig brain (anti-ChAT 2) was used under similar conditions. These treatments had no effect on noradrenaline uptake and did not release glutamate decarboxylase. The results suggest selective lysis of cholinergic synaptosomes had occurred. A similar selective lysis was also observed when synaptosomes prepared from guinea pig cerebral cortex were used. Anti-ChAT 2 also inhibited choline uptake in a complement-independent manner.
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PMID:A cell-surface antigen of cholinergic nerve terminals recognized by antisera to choline acetyltransferase. 377 30

Young (8 month) and aged (27-28 month) male C57BL/6J mice were trained in a spatial discrimination task requiring working memory. The mice were tested during three trials daily in an eight-arm radial maze for 36 test days. Correct choices were reinforced with isotonic saline. In contrast to past reports, young mice learned the task. Old mice also learned the task, and no significant age-related differences in performance were observed. Following maze training, the mice were killed, the brains removed, and the specific activities of choline acetyltransferase (E.C.2.3.1.6., ChAT) and L-glutamic acid decarboxylase (E.C.4.1.1.15., GAD) were assayed in the hippocampus, and in frontal, sensorimotor, and cingulate areas of the cerebral cortex. The activities of these neurotransmitter synthetic enzymes did not differ significantly between young and old mice. Correct responding in the radial maze was positively correlated to ChAT activity in the cingulate cortex and negatively correlated to ChAT activity in the sensorimotor cortex. There was a similar pattern of correlation between performance and regional GAD activity, although none of the correlations involving GAD reached statistical significance.
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PMID:Radial maze performance in young and aged mice: neurochemical correlates. 398 22

Activities of the neurotransmitter synthetic enzymes, choline acetyltransferase (EC 2.3.1.6; ChAT), glutamic acid decarboxylase (EC 4.1.1.15; GAD), and tyrosine hydroxylase (EC 1.14.3.2; TH), were assayed in four brain regions of A/J and C57BL/6J mice at three ages (4, 18, and 24 months). The brain regions assayed were the fronto-parietal cortex, hippocampus, striatum, and cerebellum. Strain effects: In some brain regions, at several ages, ChAT activity did not differ among the two strains. However, ChAT was higher in the C57BL/6J strain in the cortex at 18 months, the hippocampus at 18 and 24 months, the striatum at 24 months, and the cerebellum at 4 months. The reverse was true in the cerebellum at 24 months, where ChAT was higher in A/J mice. GAD activity in C57BL/6J mice compared to that of A/J mice was higher in the striatum and cortex, and lower in the hippocampus and cerebellum. TH activities in all four regions were generally higher in C57BL/6J mice than in A/J mice. Age effects: Age differences in enzyme activities varied with the genetic strain. ChAT activity generally was higher in brain regions of older mice of both strains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Age and strain comparisons of neurotransmitter synthetic enzyme activities in the mouse. 613 17

In this study the effect of the anti-inflammatory drugs indomethacin, ibuprofen, ebselen (PZ 51, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one), and BW755C (3-amino-1-(m-(trifluoromethyl-phenyl)-2-pyrazoline) on kainic acid (KA)-induced behavioral and neurochemical changes in rats was investigated. Rats injected with KA (10 mg/kg s.c.) developed seizure activity with a 20% mortality within the first 4 h and neuronal degeneration in the limbic system after 3 days. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg/kg i.p.) augmented KA-induced epileptic activity and increased the mortality in status epilepticus to 80%. Another cyclooxygenase inhibitor, ibuprofen (20 mg/kg i.p.), and the lipoxygenase inhibitor ebselen (20 mg/kg i.p.) showed no effect on KA-induced symptoms and neurochemical changes. Application of the cyclooxygenase/lipoxygenase inhibitor BW755C (40 mg/kg i.p.) reduced the severity of seizures and protected significantly from irreversible brain lesions induced by KA. The marked reduction of glutamate decarboxylase (GAD; 53.3 +/- 12.2% of control) and choline acetyltransferase (ChAT; 60.9 +/- 9.1% of control) activities in amygdala/pyriform cortex and GAD activity in hippocampus (69.4 +/- 5.6% of control) observed 3 days after KA injection was abolished by BW755C treatment. Histopathological analyses of brain tissue showed that treatment with BW755C prevented the KA-induced nerve cell degeneration, edema, hemorrhages, and tissue necrosis in amygdala/pyriform cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The cyclooxygenase and lipoxygenase inhibitor BW755C protects rats against kainic acid-induced seizures and neurotoxicity. 806 64

The medial septum and nucleus of the diagonal band (MS/nDB) contain cholinergic and GABAergic neuronal populations that have been identified based on immunohistochemical staining and/or electrophysiological properties. We explored the molecular diversity of MS/nDB neurons using single-cell reverse transcription-polymerase chain reaction (scRT-PCR) to assess gene expression profiles during aging in individual neurons acutely isolated from young (2-4 months) and aged (26-27 months) F344 rats. Neuronal gene expression profiles were characterized by detection of mRNAs for choline acetyltransferase (ChAT, cholinergic) and glutamate decarboxylase (GAD67, GABAergic), as well as mRNAs for calcium binding proteins (CaBPs) calbindin-D28k, calretinin and parvalbumin. Four major neuronal populations were identified: ChAT-positive (ChAT+) cells, GAD-positive (GAD+) cells, ChAT+/GAD+ cells and ChAT negative/GAD negative (ChAT-/GAD-) cells. With age, the percentage of cells expressing ChAT mRNA decreased from 53% in young to 40%, and the expression of GAD67 mRNA was reduced from 56 to 35% of the cells tested. The percentage of cells with detectable levels of both ChAT and GAD67 mRNA was reduced from 24% in young to 9% in aged. Concomitantly, the percentage of ChAT-/GAD- cells increased from 15 to 34% with age. Of the CaBPs, calretinin expression was observed most frequently in this study, and its detection decreased from 33 to 22% of the cells with age. Observations concerning the CaBPs were confirmed using in situ hybridization. These results suggest a shift in the mRNA expression profiles of MS/nDB neuronal populations during aging and exemplify the molecular diversity of cholinergic and GABAergic cells.
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PMID:Single-cell RT-PCR detects shifts in mRNA expression profiles of basal forebrain neurons during aging. 1183 97

Rats with different degrees of microencephaly were obtained by injecting pregnant mothers with methylazoxymethanol acetate (MAM) at gestational days 13.5 or 16.5. Specific markers for cholinergic (choline acetyltransferase, ChAT), GABAergic (glutamate decarboxylase, GAD), and glutamatergic (D-3H aspartate high affinity uptake) neurons, were measured in several brain regions (cortex, hippocampus, anterior and posterior striatum, medial septum plus nucleus of the diagonal band, globus pallidus) in young and adult microencephalic rats. In adult rats born to mothers injected with MAM at gestational day 16.5 (G16.5) ChAT level was increased in the cortex, hippocampus and striatum but decreased in the septal complex; GAD was decreased in the globus pallidus and, to a little extent, in the hippocampus while D-3H aspartate uptake was decreased in the striatum. One month old rats belonging to the same group showed comparable differences with the exception of larger increase of ChAT in the cortex and striatum. In adult rats born from mothers injected with MAM at gestational day 13.5 (G13.5) differences in the cholinergic marker were in general less pronounced; GAD was not decreased in the globus pallidus and D-3H aspartate uptake was unchanged in the striatum but significantly decreased in the hippocampus. The results are correlated with morphological brain alterations caused by differentially timed MAM treatment and with available information on the generation time of various neuronal populations. They show that the balance between different neurotransmitter systems can be experimentally altered and suggest that MAM treatment may provide an experimental tool for studying the development of this balance.
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PMID:Regional- and Age-Specific Neurochemical Alterations in Rats Rendered Microencephalic by Differentially Timed Gestational Methylazoxymethanol Treatment. 1210 22

Neurons of the basal forebrain (BF) possess unique combinations of voltage-gated membrane currents. Here, we describe subtypes of rat basal forebrain neurons based on patch-clamp analysis of low-voltage activated (LVA) calcium and tetrodotoxin-resistant (TTX-R) sodium currents combined with single-cell RT-PCR analysis. Neurons were identified by mRNA expression of choline acetyltransferase (ChAT+, cholinergic) and glutamate decarboxylase (GAD67, GABAergic). Four cell types were encountered: ChAT+, GAD+, ChAT+/GAD+ and ChAT-/GAD- cells. Both ChAT+ and ChAT+/GAD+ cells (71/75) displayed LVA currents and most (34/39) expressed mRNA for LVA Ca(2+) channel subunits. Ca(v)3.2 was detected in 31/34 cholinergic neurons and Ca(v)3.1 was expressed in 6/34 cells. Three cells expressed both subunits. No single neurons showed Ca(v)3.3 mRNA expression, although BF tissue expression was observed. In young rats (2-4 mo), ChAT+/GAD+ cells displayed larger LVA current densities compared to ChAT+ neurons, while these latter neurons displayed an age-related increase in current densities. Most (29/38) noncholinergic neurons (GAD+ and ChAT-/GAD-) possessed fast TTX-R sodium currents resembling those mediated by Na(+) channel subunit Na(v)1.5. This subunit was expressed predominately in noncholinergic neurons. No cholinergic cells (0/75) displayed fast TTX-R currents. The TTX-R currents were faster and larger in GAD+ neurons compared to ChAT-/GAD- neurons. The properties of ChAT+/GAD+ neurons resemble those of ChAT+ neurons, rather than of GAD+ neurons. These results suggest novel features of subtypes of cholinergic and noncholinergic neurons within the BF that may provide new insights for understanding normal BF function.
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PMID:Low voltage-activated calcium and fast tetrodotoxin-resistant sodium currents define subtypes of cholinergic and noncholinergic neurons in rat basal forebrain. 1583 20