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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between the susceptibility to convulsions, the content of pyridoxal 5'-phosphate and the activity of pyridoxal kinase (EC 2.7.1.35) and glutamate decarboxylase (EC 4.1.1.15) in brain, was studied in the developing mouse. Seizures were induced by pyridoxal phosphate-gamma-glutamyl hydrazone (PLPGH), a drug previously reported to reduce the levels of pyridoxal 5'-phosphate and as a consequence to inhibit the activity of glutamate decarboxylase in brain of adult mice. It was found that the seizure pattern, as well as the time of appearance of convulsions, differed between 2- and 5-day old mice and 10-day old or older mice, indicating a progressive increase in seizure susceptibility during development. In brain, pyridoxal kinase activity and pyridoxal 5'-phosphate levels were decreased by the administration of PLPGH at all ages studied, whereas glutamate decarboxylase activity was inhibited less than 25% in 2- and 5-day old mice, and about 50% thereafter. Parallelly, the activation of glutamate decarboxylase by pyridoxal 5'-phosphate added in vitro to control homogenates was less in 2- and 5-day old mice than in older animals. It is concluded that the increase in the susceptibility to seizures induced by PLPGH during development is probably related to the increase observed in the sensitivity of glutamate decarboxylase in vivo to a decrease of pyridoxal 5'-phosphate levels. The correlation between pyridoxal 5'-phosphate, glutamate decarboxylase, and seizure susceptibility seems to be established at about 10 days of age.
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PMID:Seizure susceptibility in the developing mouse and its relationship to glutamate decarboxylase and pyridoxal phosphate in brain. 17 40

The activity of the dissociative anaesthetics ketamine and gamma-hydroxybutyrate against seizures induced by mercaptopropionate and pentylenetetrazol have been determined. Ketamine (90 mg/kg) prevented the seizures induced by both convulsants, but gamma-hydroxybutyrate had negligible anticonvulsant activity. Mercaptopropionate (150 mg/kg) produced a rapid fall in whole brain glutamate decarboxylase activity which correlated with the onset of convulsions. Ketamine given prior to the mercaptopropionate prevented the convulsions, but had no effect on the reduction of enzyme activity. It was concluded that although ketamine was an anticonvulsant it did not act by preventing the inhibition of glutamate decarboxylase responsible for mercaptopropionate-induced convulsions.
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PMID:The anticonvulsant activity of ketamine agains siezures induced by pentylenetetrazol and mercaptopropionic acid. 97 26

The effects of DL-penicillamine (DL-PeA), hydrazine and toxopyrimidine (TXP, 2-methyl-6-amino-5-hydroxymethylpyrimidine) on gamma-aminobutyric acid (GABA) metabolism in mouse brain were studied. All these compounds inhibited the activity of glutamate decarboxylase [EC 4.1.1.15] (GAD) and slightly inhibited that of 4-aminobutyrate: 2-oxoglutarate aminotransferase [EC 2.6.1.19] (GABA-T). In contrast, very different effects were observed on GABA levels; hydrazine caused a marked increase, DL-PeA had no effect, and TXP caused a slight decrease in the content of the amino acid. These results could be described by an equation which related the excitable state to changes in the flux of the GABA bypass. Since the values obtained from the equation clearly reflect the seizure activity, it is suggested that the decreased GABA flux might be a cause of convulsions induced by these drugs.
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PMID:A correlation between changes in gamma-aminobutyric acid metabolism and seizures induced by antivitamin B6. 100 83

The basket cells are an important cell type in the dentate gyrus because their axon terminals form a prominent plexus with the somata of the principal cells, the granule cells. The basket cells consist of five morphological types that have different dendritic arborizations and somal positions. All five types of basket cell display immunoreactivity for glutamate decarboxylase, the synthesizing enzyme for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Electron microscopy has shown that basket cells have similar ultrastructural features including smooth dendrites, infolded nuclei, intranuclear rods, prominent Nissl bodies, and a thick rim of perikaryal cytoplasm. The axon terminals of basket cells form symmetric synapses with the somata and proximal dendrites of granule cells. Since the somata, basal dendrites and proximal apical dendrites of basket cells are postsynaptic to granule cell axon collaterals, the basket cells are linked to granule cells in a powerful feedback inhibitory circuit. The basket cells are also involved in feedforward inhibition as a result of being postsynaptic to perforant path and commissural axons. The calcium-binding protein, parvalbumin, is found in each type of basket cell but less than 40% of the basket endings display parvalbumin-immunoreactivity. In contrast, virtually all cortical basket cells contain parvalbumin, and this difference for basket cells between neocortex and hippocampus may contribute to the lower seizure threshold for the hippocampal formation as compared to the neocortex. Studies show that basket cells play a role in at least two experimental models of epilepsy.
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PMID:Local circuitry of GABAergic basket cells in the dentate gyrus. 133 68

We recently reported that the mammalian brain has two forms of the GABA synthetic enzyme glutamate decarboxylase (GAD, E.C. 4.1.1.15), which are the products of two genes. The two forms, which we call GAD65 and GAD67, differ from each other in sequence, molecular size, subcellular distribution, and interactions with the cofactor pyridoxal phosphate (PLP), with GAD65 activity more dependent than that of GAD67 on the continued presence of exogenous PLP. The existence of two GAD genes suggests that individual GABA neurons may be subject to differential regulation of GABA production. We have examined the expression of these two forms of GAD during postnatal development of the rat striatum to determine whether different classes of GABA neurons selectively express different amounts of the two GAD mRNAs. Here we present evidence for a dramatic developmental difference in the expression of the two mRNAs during postnatal development of the rat striatum. Using in situ hybridization to the two GAD mRNAs, we observed a selective increase in GAD65 mRNA during the second postnatal week, at the time when striatal matrix neurons innervate the substantia nigra (SN). PLP-dependent enzyme activity in the midbrain increases in parallel with increased expression of GAD65 mRNA in the striatum. We hypothesize that the innervation of the SN by striatal neurons triggers an increase in GAD65. The changing ratios of GAD65 and GAD67 in the striatum may contribute to the well-documented changes in seizure susceptibility that occur in early life.
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PMID:Transient increase in expression of a glutamate decarboxylase (GAD) mRNA during the postnatal development of the rat striatum. 151 45

The anticonvulsant effects of felbamate alone or in combination with diazepam were investigated against maximal electroshock-, pentylenetetrazol-, isoniazid- and bicuculline-induced seizures in mice. A single subprotective dose of felbamate, a dose which offers no protection to animals when combined with diazepam, enhanced the protective effects of diazepam against seizures induced by electroshock, pentylenetetrazol and isoniazid, as measured by significant reduction of ED50 values. However, felbamate failed to significantly affect the protective action of diazepam against bicuculline. Felbamate does not interact directly with the GABA-benzodiazepine-ionophore complex. Thus the enhancement of anticonvulsant activity of diazepam by felbamate against maximal electroshock and pentylenetetrazol may involve an indirect effect at benzodiazepine receptors. The anticonvulsant action of felbamate against isoniazid does not seem to involve benzodiazepine receptors and may be due to reversing the inhibitory effect of isoniazid on glutamate decarboxylase (GAD) activity. The interaction between felbamate and diazepam may also involve other mechanisms.
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PMID:Interaction of felbamate and diazepam against maximal electroshock seizures and chemoconvulsants in mice. 166 5

In order to determine whether calcium binding protein (calbindin-D28k or CaBP) and glutamate decarboxylase (GAD) may be involved in the process underlying the generation of seizure activity, changes in CaBP protein and mRNA and in GAD mRNA were examined in the kindling model of epilepsy. Following amygdaloid (AK) and commissure (CK) kindling significant decreases in the concentration of CaBP of 20% and 30%, respectively, were specifically observed in the hippocampal formation. However, using a cDNA specific to mammalian CaBP, Northern analysis of poly(A+) RNA and slot blot analysis of total RNA revealed no changes in the levels of CaBP mRNA in hippocampus, subcortical area (including amygdala, substantia nigra and striatum) or cerebellum of rats sacrificed 30 min, 1 h, 6 h or 24 h after the last kindled seizure. Similarly when these blots were reprobed with a cDNA specific to mammalian GAD, no changes in GAD gene expression were observed. However, fos gene expression was markedly enhanced at 1 h after seizure. We also tested whether changes in CaBP or GAD mRNA could be detected at any of the various stages of the kindling process. Slot blot analysis of cortex, subcortical structures and hippocampus revealed no changes in CaBP or GAD mRNA during the course of commissure kindling. In situ hybridization studies with GAD and CaBP 35S-labeled antisense probes also indicated no obvious changes upon visual analysis of autoradiographs. However, when silver grains were counted, significant changes in GAD mRNA in individual cells in hippocampus and substantia nigra were noted after kindling induced epilepsy. Our results indicate that, unlike fos gene expression, prominent alterations in GAD and CaBP mRNA in gross brain regions (as measured by slot blot and Northern blot analyses) are not observed in the kindling process. However, our in situ hybridization studies suggest that changes in GAD mRNA in individual cells may be involved in the process underlying kindling induced seizure activity.
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PMID:Calcium binding protein (calbindin-D28k) and glutamate decarboxylase gene expression after kindling induced seizures. 170 39

Because previous work showed that in the newborn brain, but not in the adult brain, glutamate decarboxylase (GAD) is notably susceptible to heat, we have studied the possible involvement of GAD inhibition in febrile convulsions and the related changes in gamma-aminobutyric acid (GABA) content. Rats of different ages were subjected to hyperthermia, and GAD activity was determined in brain homogenates by measuring the release of 14CO2 from labeled glutamate and by measuring the formation of GABA. The latter method gave considerably lower values than the former in the youngest rats, and was considered more reliable. With this method, we found a 37-48% inhibition of GAD activity in rat pups 2-5 days old, which showed febrile seizures at progressively higher body temperatures, whereas in 10- and 15-day-old animals, which did not show convulsions, GAD activity was not affected by hyperthermia. Whole-brain GABA levels, however, did not change at any age. In contrast to GAD, choline acetyltransferase and lactic dehydrogenase activities were not altered by hyperthermia at any of the ages studied. These results suggest that a decreased efficiency of the inhibitory neurotransmission mediated by GABA, consequent to the inhibition of GAD activity, may be a factor related to febrile convulsions.
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PMID:Inhibition of brain glutamate decarboxylase activity is related to febrile seizures in rat pups. 172 43

The influence of anticonvulsant treatment upon (1) chronically increased seizure susceptibility, (2) on late increases in peptide levels and (3) on seizure-induced brain damage was investigated during various stages of acute kainic acid (10 mg/kg i.p.)-induced seizures. The seizures were interrupted at various stages of the syndrome (50 min to 24 h after injection of the toxin) by injecting thiopental (50 mg/kg i.p.) or the excitatory amino acid antagonist, MK-801 (10 mg/kg i.p.). The increase in neuropeptide Y and somatostatin levels in the frontal cortex could be prevented by early injection of either anticonvulsant (up to 180 min after kainic acid). No protection against the increase in peptide levels was observed when the anticonvulsants were applied later. Kainic acid-induced neuronal damage in the amygdala, with glutamate decarboxylase as a neurochemical marker, was entirely prevented by interrupting seizures up to 2 h after kainic acid. Partial protection (about 40-50%) was even found when the anticonvulsant treatment was applied after the acute syndrome, as late as 8 h after kainic acid injection. Chronically increased seizure susceptibility induced by kainic acid was not prevented, even by early injection (90 min after kainic acid) of the anticonvulsant drugs. The data indicate that (1) the late increase in seizure susceptibility may be initiated early after injection of kainic acid. (2) the late increase in peptide levels may be related to the frequency of acute seizures rather than to a change in seizure threshold or brain damage and (3) even late anticonvulsant therapy may antagonize seizure-induced brain damage in the amygdala.
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PMID:Effect of anticonvulsant treatment on kainic acid-induced increases in peptide levels. 197 15

Behavioral changes following injury, neural degeneration, and aging partly reflect the synaptic plasticity of the nervous system. Such long-term plastic changes are likely to depend on alterations in the production of proteins involved in synaptic structures and neurotransmission. We have studied the regulation of the mRNA encoding one such protein, glutamate decarboxylase (GAD), the rate limiting enzyme of GABA synthesis, after a unilateral lesion in the hippocampus that leads to increased seizure susceptibility. Quantitative in situ hybridization reveals a long-term increase in GAD mRNA in several bilateral structures, as well as in specific neurons in the ipsilateral dentate gyrus. Our data do not support the often stated hypothesis that seizure susceptibility depends on the malfunction of GABA neurons.
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PMID:Long-term increase of glutamate decarboxylase mRNA in a rat model of temporal lobe epilepsy. 197 15


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