Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since glutamine synthetase (GS) has been proposed as the primary enzyme in the regulation of glutamate metabolism in the central nervous system and since inhibition of the activity of this enzyme in vivo leads to seizures, it has been proposed that an abnormality in the structure or function of this enzyme could be responsible for the induction of seizures in epilepsy prone rats. To test this hypothesis the glutamine synthetases were purified from the brains of both genetically epilepsy prone rats (GEPR) and their progenitors, genetically epilepsy resistant rats (GERR). The enzymes were compared using both SDS-PAGE and isoelectric focusing. The immunoreactivities of equal amounts of protein were determined using the ELISA technique, and the regulation of the glutamine synthetase activities by Mn2+/Mg2+ ratios were compared. The only difference found between the glutamine synthetases from the two strains was a slightly lower specific activity of the enzyme from the epilepsy prone animals.
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PMID:Comparison of glutamine synthetases from brains of genetically epilepsy prone and genetically epilepsy resistant rats. 135 42

The purpose of this study was to determine the effects of two experimental models of chronic epilepsy in rats on the activity of the astroglial enzyme glutamine synthetase. FeCl2-induced cortical lesions that increased the sensitivity to pentylenetetrazol-induced generalized seizures also significantly increased glutamine synthetase activity in the homotopic site of the contralateral cortex. A decrease in cortical glutamine synthetase was found in the cortex ipsilateral to the stimulated amygdala in electrically kindled animals. These findings provide evidence that increased glutamine synthetase activity is associated with developing, submaximal seizures and that decreased activity is characteristic of mature, chronic seizure states such as that associated with kindled amygdala seizures.
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PMID:Alterations in glutamine synthetase activity by FeCl2-induced focal and kindled amygdaloid seizures. 196 96

Kainic acid was injected into the hippocampus of rats and glutamine synthetase was measured to determine whether astrocytes are involved in the early effects of this neurotoxic agent. Glutamine synthetase was reduced by 38%, 24 h after the stereotaxic application of 4 nmol of kainic acid to this region. The reduction in glutamine synthetase by kainic acid was not due to direct inhibition of the brain enzyme. This effect also was not due to seizure activity since rats peripherally injected with a convulsant dose of kainic acid were found to have normal hippocampal glutamine-synthetase activity. Exposure of astrocyte cultures to kainic acid for 24 h produced no evidence of gliotoxicity and no change in glutamine synthetase activity. The effect of intrahippocampal kainic acid on glutamine synthetase appears to be indirect, most likely produced secondarily to its neuronal effects. Several studies have shown that endogenous glutamate is involved in kainate neurotoxicity. A reduction in glutamine synthetase by kainic acid may impair the capacity for astrocytes to metabolize glutamate. Such an impairment could contribute to the glutamate-mediated cell death following kainic acid exposure.
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PMID:Intrahippocampal kainic acid reduces glutamine synthetase. 197 Jun 31

1. Seizure prone (SP)-gerbils (Meriones unguiculatus) tested repeatedly in an open field exhibited habituation of seizures after one or two trials and subsequently showed more ambulatory activity than non-seizure prone (NSP) individuals. 2. A subset of 5 SP and 5 NSP animals were killed and portions of each cerebral hemisphere, the cerebellum and the brainstem medulla were analysed for glutamine synthetase (GS). 3. GFAP immunohistochemistry was used on forebrain sections to assay astrocyte density. 4. It was found by MANOVA, PCA and regression analyses that seizures and ambulatory activity were related to a deficiency in cerebral GS. 5. Rearing behaviour was related to medullary brainstem and cerebellar GS concentrations. 6. The decreased GS of the seizure-prone gerbils was not apparently associated with a deficiency of astrocytes, perhaps the reverse. 7. The results are discussed in relation to glial-neuronal interactions modulating arousal and the propensity for seizures.
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PMID:Seizures in the Mongolian gerbil are related to a deficiency in cerebral glutamine synthetase. 257 78

The effect of administration of chlorpromazine on the activity of glutamine synthetase and glutaminase and the content of glutamate and gamma-aminobutyric acid (GABA) in different regions of rat brain was studied in an investigation of the possible role of these amino acids in the lowering of the seizure threshold following prolonged administration of chlorpromazine. Chlorpromazine was administered at a dose of 20 mg/kg of body weight s.c. For the acute study, the animals were killed 20 min after a single injection. For the long-term study, the animals were treated every day with the same dose for 21 days and were killed 20 min after the last injection. The results showed an increase in glutamate level in each brain region investigated following long-term administration, but only in the cerebral cortex after a single dose. GABA levels showed an increase in the brainstem only in acute experiments. Glutamine synthetase activity was increased in all three regions after a single dose and only in cerebral cortex after long-term administration. Glutaminase activity showed a decrease in cerebral cortex only after long-term administration of the drug. These results suggest the possible occurrence of a state of increased excitability in the brain as a result of long-term administration of chlorpromazine, thus contributing to the known complication of seizures.
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PMID:Acute and long-term effects of chlorpromazine on glutamine synthetase and glutaminase in rat brain. 288 78

The forebrain content of several rat brain synaptic proteins (synaptin, D1, D2, and D3) was reduced in rats receiving electroconvulsive seizures on days 2-11, 9-18, or 19-28 and sacrificed at the age of 30 days. Forebrain weight, total protein, and the glial enzyme glutamine synthetase were also decreased, whereas the neuronal enolase 14-3-2 was unchanged. The findings suggest that seizures in the immature rat brain resulted in a parallel reduction of synaptic material and of the amount of glial cells. The increased concentration of the enolase 14-3-2 found in rats seizured on days 19-28 may reflect the high demands on the glycolytic system during the seizures.
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PMID:Synaptic proteins after electroconvulsive seizures in immature rats. 610 6

The cerebral concentrations of pyridoxal-5'-phosphate and divalent transition metal ions (Cu2+ and Zn2+) are appreciably higher in the seizure-susceptible strain of mouse (DBA/2J) than those in normal strains (CBA/Ca and Parkes ). By injecting metal ions intracranially and pyridoxal-5'-phosphate intraperitoneally, we could render the normal mouse prone to sound-induced epilepsy. The behaviour of the treated seizure-susceptible strain of mouse. The levels of glutamate and aspartate in its inferior colliculus were elevated and the concentration of gamma-aminobutyrate was lowered. Glutaminase inhibitors, 6-diazo-5-oxo-L-norleucine (DON) and 0-diazo-acetyl-L-serine (azaserine), and a transaminase inhibitor, 4-amino-3- isoxazolidone (L-cycloserine), when injected intraperitoneally, protected the seizure-susceptible mouse from undergoing convulsions, whereas pyridoxal-5'-phosphate and methionine sulphoximine, a glutamine synthetase inhibitor, exacerbated its epileptic condition. We propose a possible sequence of biochemical events associated with susceptibility to audiogenic seizures.
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PMID:Studies on sound-induced epilepsy in mice. 614 59

Previous investigations in seizure-prone mice have suggested that an abnormally elevated production of the astrocyte-derived neuroexcitant, quinolinic acid (QUIN), plays a role in seizure susceptibility. In order to evaluate further the role of QUIN metabolism in genetic murine seizure models, the activities of its biosynthetic enzyme 3-hydroxyanthranilic acid oxygenase (3HAO), and of two other astrocytic enzymes, kynurenine aminotransferase (KAT) and glutamine synthetase (GS), were measured in the brains of seizure-prone EL and DBA/2 mice and two non-epileptic strains (BALB/c and Swiss-Webster). 3HAO activity was found to be markedly higher in both EL and DBA/2 mice than in the non-epileptic strains in all brain regions examined. The activity of 3HAO was not modified by the tossing procedure employed to promote seizures in EL mice. While some strain differences were noted in the activities of KAT and GS, these enzymes did not distinguish seizure-prone from the non-epileptic mice. In order to delineate better the relationship between glial activation and 3HAO, KAT and GS, further studies were performed in the ibotenate-lesioned hippocampus. In mice (but not in rats), the activity of 3HAO was selectively increased in gliotic tissue. These data demonstrate substantial species and strain differences in astroglial enzymes and in their response to brain injury. The observation of widespread abnormally high 3HAO activity in two distinct seizure-prone mouse strains strengthens the hypothesis that enhanced production of QUIN contributes to seizure susceptibility in mice.
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PMID:Differential expression of the astrocytic enzymes 3-hydroxyanthranilic acid oxygenase, kynurenine aminotransferase and glutamine synthetase in seizure-prone and non-epileptic mice. 780 40

Human and experimental animal studies suggest a relationship between low Mn status and seizures. The genetically epilepsy prone rat (GEPR), which has low tissue Mn levels, was studied in the context of Mn supplementation. Manganese was provided at 45 micrograms/g diet (control) or 1000 micrograms/g diet (supplemented) to dams during pregnancy and lactation, then to the offspring after weaning. Offspring were tested for seizure susceptibility as young adults; tissue trace elements, brain monoamines and brain glutamine synthetase activity were measured as endpoint biochemical indices. Supplementation, although developmentally encompassing and highly effective in elevating tissue Mn levels, had no effect on seizure latency or severity. Similarly, brain monoamine concentrations and glutamine synthetase activities were resistant to Mn supplementation. Notably, the GEPR was confirmed to have low whole brain glutamine synthetase activity. These findings suggest that seizure activity in the GEPR does not stem from an increased nutritional/metabolic need for Mn.
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PMID:The influence of manganese supplementation on seizure onset and severity, and brain monoamines in the genetically epilepsy prone rat. 809 51

Low blood manganese (Mn2+) concentration is associated with epilepsy in humans and rats. The low Mn2+ concentration is attributed by some investigators to the seizure activity associated with the epilepsy, whereas others propose that the low Mn2+ concentration may be secondary to genetic mechanisms underlying the epilepsy. To begin to differentiate between these possibilities, Mn(2+)-binding enzymes of liver and brain (i.e., arginase and glutamine synthetase, respectively) were assayed in rats exposed to chronically induced seizures and in genetically epilepsy-prone rats (GEPRs). Chronic seizures caused a decrease in whole blood Mn2+ levels but did not affect brain Mn2+ concentrations. Arginase activity was increased in livers of rats with chronic seizure as compared with controls, but this difference was eliminated when Mn2+ was added to the assay. Brain glutamine synthetase activity was unaffected by chronic seizures, but the activity of this enzyme was significantly lower in GEPR brain than in control brain. Liver arginase activity tended to be lower in GEPRs, although the difference was not statistically significant. These data indicate that seizures affect liver arginase activity through changes in liver Mn2+ concentration, but GEPRs show abnormalities in Mn(2+)-dependent enzymes apparently independent of seizure activity.
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PMID:Manganese and epilepsy: brain glutamine synthetase and liver arginase activities in genetically epilepsy prone and chronically seizured rats. 809 25


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