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)

We have examined the influence of strychnine-insensitive glycine (gly2) receptor agonists and antagonists on the expression of generalized seizure activity (generalized seizure threshold (GST), afterdischarge duration and motor seizure response) in fully amygdala kindled rats. Intra-amygdaloid administration of the selective gly2 receptor antagonist, 7-chlorokynurenic acid (7-C1KYN) (10-50 nmol) dose-dependently raised GSTs in a glycine-reversible manner. The same doses had no significant effect on other parameters of seizure expression. (+/-)-3-Amino-1-hydroxy-2-pyrrolidone (HA-966), a proposed low-efficacy partial agonist at the gly2 receptor17, showed similar but weaker anticonvulsant activity in this model. The active, R-(+)-enantiomer of HA-966 showed greater anticonvulsant efficacy than the racemic mixture, but was still clearly less active than 7-C1KYN. The gly2 receptor agonists glycine (10-50 nmol), D-serine (50 nmol) and D-alanine (50 nmol) failed to influence any of the parameters of the seizure response, suggesting that gly2 receptors in the basolateral amygdala are fully saturated in vivo. The behavioural impairment induced by high doses of 7-C1KYN did not appear to be associated with gly2 receptor blockade. These results support the concept that potent and selective gly2 receptor antagonists may provide a useful, novel class of anticonvulsant agents.
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PMID:The influence of strychnine-insensitive glycine receptor agonists and antagonists on generalized seizure thresholds. 164 57

This study extends our previous work in which we described the presence of an interictal behavioral disturbance in a chronic animal model of temporal lobe epilepsy (TLE). In this study, we investigated the cerebrospinal fluid (CSF) neurotransmitter changes underlying the development of chronic recurrent seizures of temporal lobe origin and interictal behavioral disturbance in cats made epileptic after intrahippocampal injection of kainic acid (KA). Using high-performance liquid chromatography, we measured 22 putative neurotransmitter amino acids. After intrahippocampal KA injection, cats developed an initial acute period of intense seizure activity. Cisternal CSF amino acids, which were repeatedly sampled during the acute period through a permanent indwelling cannula, were unchanged apart from a mild elevation in CSF alanine. The high-level seizure activity gradually decreased, and cats entered a chronic epileptic period characterized by recurrent yet intermittent temporal lobe seizures. CSF GABA levels during the chronic epileptic period were significantly decreased. In contrast, CSF levels of other amino acids--alanine, tyrosine, taurine, aspartic acid, and glutamic acid--did not change significantly. Behavioral testing also showed a heightened interictal defensive reactivity during the chronic epileptic period. To the extent that CSF GABA concentration reflects brain GABA concentration, this study suggests that a decrease in brain GABA may contribute both to the epilepsy and interictal emotional lability of animals with a chronic seizure disorder of temporal lobe origin.
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PMID:Interictal behavioral alterations and cerebrospinal fluid amino acid changes in a chronic seizure model of temporal lobe epilepsy. 174 47

The first component of the mitochondrial electron-transport chain is especially complex, consisting of 19 nuclear and seven mitochondrion-encoded subunits. Accordingly, a wide range of clinical manifestations are produced by the various mutations occurring in human populations. In this study, we analyze the subunit structure of complex I in fibroblasts from two patients who have distinct clinical phenotypes associated with complex I deficiency. The first patient died in the second week of life from overwhelming lactic acidosis. Severe complex I deficiency was evident in her fibroblasts, since alanine oxidation was markedly reduced whereas succinate oxidation was normal. Absence of a 20-kDa subunit was demonstrable when newly synthesized proteins were immunoprecipitated from pulse-labeled fibroblasts by anti-complex I antibody. Disordered assembly or decreased stability of the complex was suggested by deficiency of multiple subunits on Western immunoblots. The second patient exhibited a milder clinical phenotype, characterized by moderate lactic acidosis and developmental delay in childhood and by onset of seizures at 8 years of age. Oxidation studies demonstrated expression of the complex I deficiency in fibroblasts, but no subunit abnormalities were detected by immunoprecipitation or Western immunoblotting. This report demonstrates the utility of cultured fibroblasts in studying mutations affecting synthesis and assembly of complex I.
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PMID:Congenital deficiency of a 20-kDa subunit of mitochondrial complex I in fibroblasts. 190 90

DL-beta-N-methylamino-alanine (DL-BMAA; 1-10 mumol i.c.v.) in mice induced a syndrome of: ataxia, ptosis, scratching, jumping, myoclonic jerks, clonic muscle spasms and tonic seizure, which was unaffected by pretreatment with D(-)-4-(3-phosphonoprop-2-enyl)-piperazine-2-carboxylate (D(-)-CPPene; i.p.), or by co-administration of gamma-D-glutamylamino-methylsulphonate (gamma-D-GAMS with DL-BMAA; i.c.v.). Pretreatment with 1-(aminophenyl)-4-methyl-7,8-methylendioxy-5H-2,3-benzodiazepine (GYKI 52466; i.v.) decreased the incidence of clonic seizures for DL-BMAA, kainic acid and RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (RS-AMPA; i.c.v.). These results suggest an involvement of the AMPA/quisqualate subtype of excitatory amino acid receptors in acute BMAA toxicity.
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PMID:Receptor site specificity for the acute effects of beta-N-methylamino-alanine in mice. 198 Feb 47

Inbred mutant El mice are highly susceptible to convulsive seizures upon "tossing" stimulation. The levels of excitatory (e.g. glutamate and aspartate) and inhibitory amino acids [e.g. gamma-amino-butyrate (GABA)] were examined in discrete regions of stimulated El mice [El(+)], non-stimulated El mice [El(-)] and ddY mice, which do not have convulsive disposition. In comparison with ddY, a general increased levels of aspartate, glutamate, glutamine, and taurine were detected in brain regions of El(-). The levels of GABA and glycine were almost the same in ddY and El(-). Compared to El(+), the levels of aspartate, glutamate, glutamine, and GABA in El(-) were either the same or higher. In the case of taurine and glycine, the levels in El(-) were either the same or lower than El(+). Alanine is special in that El(-) have a higher level than El(+) in hippocampus but lower in cerebellum. Furthermore, while marked changes were registered in several brain regions, none of the amino acids investigated showed any significant differences in the hypothalamus of three different groups of mice.
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PMID:Regional excitatory and inhibitory amino acid levels in epileptic El mouse brain. 221 61

The distribution density of opioid receptors in the brain of El mice (seizure-susceptible strain) was examined to determine the relation between seizures and the opioid system. Saturation curves and Scatchard plots of [3H]2-D-alanine-5-D-leucine enkephalin binding revealed that the opioid delta receptor density in adult El mice during interictal periods was significantly increased in the cerebral cortex, hippocampus, and septal area. It was further shown that the concentration of such receptors in 25-day-old El mice that had no seizures was also significantly increased in the hippocampus and septal area, with no changes in apparent affinities, as compared with in the corresponding regions in ddY mice (seizure-nonsusceptible strain; the mother strain of El). Such up-regulation of opioid receptors in the El mouse brain could result from deficits in endogenous opioid peptides, which could be associated with the pathogenesis of seizure diathesis in the El mouse.
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PMID:Alteration of opioid receptors in seizure-susceptible El mouse brain. 254 Apr 43

Pyruvate carboxylase deficiency results in congenital lactic acidosis. We report the significant finding in a child with infantile spasms controlled with adrenocorticotrophin hormone (ACTH) but who then developed severe lactic acidosis; pyruvate carboxylase deficiency was subsequently diagnosed. Blood lactate, pyruvate, and alanine levels were elevated, as well as cerebrospinal fluid alanine. Plasma alanine concentration was doubled by ACTH therapy. Fibroblasts contained extremely low pyruvate carboxylase activity. The patient died at 12 weeks of age after recurrent episodes of profound acidosis. At autopsy, the brain manifested cystic degeneration and demyelination. Pyruvate carboxylase deficiency is associated with neonatal onset of acidosis, delayed development, seizures, hypotonia, recurrent profound acidosis, and early death. The dramatic rise in plasma alanine content coincident with ACTH therapy suggest that ACTH played a role in precipitating the catastrophic metabolic acidosis.
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PMID:Pyruvate carboxylase deficiency: acute exacerbation after ACTH treatment of infantile spasms. 255 27

Anticonvulsant action of MK-801, a novel noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptor, was examined in genetically epileptic E1 mice. Systemic injection of MK-801 (0.1-1.0 mg/kg) potently suppressed generalized tonic-clonic convulsions of in a dose-dependent manner (ED50, 0.17 mg/kg). This anticonvulsant effect of MK-801 appeared at a dose which did not induce any obvious behavioral changes. Following the administration of a fully anticonvulsant dose of MK-801 (1 mg/kg), amino acid analysis revealed a significantly elevated level of glycine in the hippocampus. Levels of other amino acids including glutamate, aspartate, taurine, glutamine, alanine, and gamma-aminobutyrate were not changed either in the hippocampus or in the cerebral cortex. This study suggests that NMDA system may play an essential role in seizure-triggering mechanisms in E1 mouse.
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PMID:Effect of a noncompetitive antagonist (MK-801) of NMDA receptors on convulsions and brain amino acid level in E1 mice. 255 74

Injection of iron salts into the rodent cortex has been shown to cause chronic or recurrent seizures. Amino acid levels in the cerebral cortex were examined 1, 3, 6, 9, 24, 48 hours and 4 weeks after an injection of ferric chloride solution to the left sensory motor cortex of rats. Aspartate level decreased 9 and 24 hours after the injections with ferric chloride. No significant change was observed in glutamate level, though glutamine level decreased 3 and 48 hours after the injection. GABA level decreased 6 hours after the injection. On the contrary, alanine and glycine levels increased 1 and 24 hours, and 24 hours after the injection, respectively. These results suggest that these amino acid neurotransmitters are involved in the acute seizure mechanism and in the process of chronic focus formation in the iron-induced epilepsy of rats.
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PMID:Amino acid neurotransmitters in iron-induced epileptic foci of rats. 257 78

The thresholds for metrazol (pentylenetetrazol) clonic convulsions and brain gamma-aminobutyric acid contents were significantly reduced after treatment with the monoamine depletors reserpine, tetrabenazine and p-chlorophenylalanine. Moreover, alpha-methyltyrosine, and alpha-methyl-m-tyrosine also lowered metrazol threshold seizures, but had no effect on brain alpha-aminobutyric acid contents. Furthermore, neither 5-hydroxytryptophan nor tranylcypromine had a significant effect on metrazol threshold seizures or brain alpha-aminobutyric acid contents, but blocked the changes previously induced by p-chlorophenyl alanine and reserpine.
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PMID:The effect of monoamine depletors on metrazol induced convulsions and brain gamma-aminobutyric acid (GABA) contents in rats. 257 59


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