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)

Recent experimental data indicate that endogenous brain ligands for the opioid receptors such as enkephalins, beta-endorphin (beta-End) and dynorphin (Dyn) may be involved in both generalized and partial seizures. The "tottering" (tg/tg) mouse provides an electrophysiological representation of generalized spontaneous human epilepsy. These mice exhibit behavioral absence seizures with accompanying spike-wave discharges. Methionine-enkephalin (M-Enk), beta-End and Dyn levels in various regions of brain were measured by radioimmunoassay (RIA) in 15-18-week-old tg/tg and control (+/+) mice to elucidate the relation between seizures and the opioid system. beta-End and Dyn levels were similar in tg/tg and +/+ mice. However, M-Enk levels were significantly increased in the striatum, cortex, pons and medulla of the tg/tg mice. Our data suggest that in the tottering mouse model of generalized epilepsy there is an alteration of enkephalinergic pathways and not of the endorphinergic or dynorphinergic pathways.
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PMID:Increased methionine-enkephalin levels in genetically epileptic (tg/tg) mice. 168 15

The aim of the present investigation was to look for the mechanisms causing disturbances in carbohydrate metabolism during the action of the epileptogenic agent methionine sulfoximine. The levels of glucose, glycogen, and indolamines were measured in seven different regions of rat brain. Methionine sulfoximine induced a decrease in serotonin level which was roughly dose-dependent. There were no obvious changes in tryptophan and 5-hydroxyindoleacetic levels in any area. Methionine sulfoximine induced the known increase in glucose and glycogen levels. The direct precursor of serotonin. 5-hydroxytryptophan, and benserazide (a decarboxylase inhibitor) were then injected into rats in association with methionine sulfoximine. In this case, methionine sulfoximine failed to induce seizures. Moreover, the serotonin level was unchanged and the carbohydrate content did not significantly increase. There was only a rise in 5-hydroxyindoleacetic acid level. This work shows a striking parallelism between serotonin decrease and glycogen increase.
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PMID:Possible involvement of indolamines in the glycogenic effect of the convulsant methionine sulfoximine in rat brain. 169 79

The effects of systemic kainic acid (KA) administration on hippocampal levels of prodynorphin and proenkephalin mRNA, as well as opioid peptides derived from these precursors, were evaluated. A single subcutaneous injection of KA induced a range of seizure states, from mild wet dog shakes to generalized motor seizures. Northern blot analysis of hippocampal mRNA revealed an increase in both prodynorphin and proenkephalin mRNA levels which corresponded to the intensity of the convulsions. Conversely, hippocampal levels of immunoreactive dynorphin A (1-8) and [Met]5-enkephalin were decreased as a function of seizure frequency and intensity. The time course of KA-induced alterations in prodynorphin and proenkephalin mRNA and peptide levels was also investigated. Hippocampal prodynorphin mRNA levels rose at a dramatic rate. At 3 h following KA administration, mRNA levels were maximally elevated approximately 13-fold. The levels decreased over a 48 h period, eventually reaching control values. In contrast, proenkephalin mRNA levels increased more slowly. At 24 h, a maximal 24-fold increase was observed. At 72 h after injection, proenkephalin mRNA levels were still slightly elevated. In the same experiment, immunoreactive enkephalin peptide levels, although somewhat decreased at 3-12 h, began to increase between 12 and 24 h after injection, and were still rising at 72 h. In marked contrast, immunoreactive dynorphin peptide levels ranged from 40% to 80% of control values at all times tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Systemic administration of kainic acid differentially regulates the levels of prodynorphin and proenkephalin mRNA and peptides in the rat hippocampus. 185 80

A case of adult pilocytic astrocytoma in the right temporal lobe is reported here. The patient was a twenty-four year old man, who came to the neurological division of our hospital on October 6, 1987 because of repeated consciousness-loss attacks accompanied with uncinate fit. He had no neurological deficits. However, an EEG revealed spike-and-wave complexes in the right temporal region, and a CT scan showed a small cystic lesion in the right temporal lobe. A diagnosis of psychomotor seizure was made, and the administration of anticonvulsants was started. The incidence of attack then decreased, but after approximately two years of drug therapy the attacks increased again. A CT scan was again performed, and revealed that the lesion in the right temporal lobe was enlarging. Also a noticeable enhanced lesion, identified as a mural nodule was found in the post-contrast enhancement study. A brain tumor was then suspected, and he was admitted to the neurosurgical division on October 11, 1989. He had no neurological deficits on admission. An MRI showed a low intensity lesion in the T1 weighted image, and a high intensity lesion in the T2 weighted image. A cystic lesion with a marked enhanced mural nodule was also found in the base of the right temporal lobe, according to the Gd enhancement study. Perifocal edema was not recognized. Cerebral angiography showed no positive findings. Positron emission tomography (PET), using H2(15)O, revealed low perfusion at or around the lesion, and PET using [11C]-methionine revealed an accumulation of methionine at the lesion. A diagnosis of low-grade glioma was made, and a right temporal craniotomy, for the purpose of totally removing the tumor was performed on October 26, 1989.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of adult pilocytic astrocytoma in the right temporal lobe]. 189 Oct 62

This work shows that the convulsant methionine sulfoximine induces an increase in glucose and glycogen levels and a parallel decrease in norepinephrine and dopamine levels in rat brain. Among the epileptogenic agents, methionine sulfoximine is known to have a glycogenic property in the central nervous system. The aim of this work is to look for the neurochemical mechanism underlying this property. For this, catecholamines, glucose, and glycogen were measured at the same time in different areas of the brain in rats submitted to methionine sulfoximine. The convulsant induced an increase in glucose and glycogen levels as previously described and a decrease in dopamine and norepinephrine levels in all the areas of the rat brain. These changes were roughly dose dependent. When L-dihydroxyphenylalanine and benserazide (a decarboxylase inhibitor) were administered with methionine sulfoximine, the latter failed to induce seizures in rat up to 8 h after dosing. Moreover, the glucose and glycogen amounts did not increase. In all these experiments, there was an obvious evidence of parallelism between seizures, increase in carbohydrate levels, and decrease in catecholamine levels. These results allow to conclude that the glycogenic property of methionine sulfoximine in the central nervous system probably results from its ability to decrease norepinephrine and dopamine levels. Because the effect of the convulsant on the catecholamine levels persisted for long, it is normal that glucose and glycogen levels increased during preconvulsive, convulsive and postconvulsive period. Methionine sulfoximine is probably glycogenic in rat brain because it decreases catecholamine levels for a long time.
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PMID:Correlation between carbohydrate and catecholamine level impairments in methionine sulfoximine epileptogenic rat brain. 227 99

Homocystinuria is an inborn error of methionine metabolism, of which cause is mainly deficiency of cystathionine synthetase. The major clinical manifestations of homocystinuria are mental retardation, seizures, ectopia lentis, skeletal deformities and occlusive vascular disease. A case of homocystinuria accompanied with deep cerebral venous thrombosis was reported. A 29-year-old woman was admitted to our hospital with unconsciousness and tetraparesis on December 7, 1984. She was diagnosed as homocystinuria due to cystathionine synthetase deficiency at 13-year-old. Amino acid analysis of serum revealed homocystinaemia (1.37 mg/dl, normal 0), hypermethioninaemia (1.27 mg/dl, normal 0.2-0.48) and low cystathionine content. CT scan revealed intraventricular hemorrhage and diffuse low density in basal ganglia and white matter. Cerebral angiograms showed that deep cerebral veins and superior sagittal sinus can not be recognized clearly in any phase, and Sylvian veins are opacified markedly. It is suggested that intraventricular hemorrhage, and low density area in basal ganglia and white matter is due to hemorrhagic infarction by venous thrombosis of internal cerebral vein. The major clinical manifestations of homocystinuria result from the elevated plasma homocysteine level. The excitotoxic effect of homocysteic acid accounts for mental retardation and seizures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Homocystinuria accompanied with cerebral deep venous thrombosis--a case report]. 236 35

Using amygdaloid kindling in chronic rats, we were able to observe behavioral, electrographic and IR-Met- and IR-Leu-enkephalin changes throughout the progress of different stages of convulsive activity. Rats presenting the initial stages of kindling, rats presenting the first generalized motor seizure, and rats with at least 10 generalized seizures were sacrificed 24 h after the last stimulus; also rats with at least 10 generalized seizures but sacrificed 21 days after the last seizure were compared with control and sham-operated groups of rats. The IR-Met and IR-Leu enkephalin concentrations in each group were measured in the striatum, amygdala, hypothalamus, medulla oblongata (including pons), hippocampus, mid-brain, spinal cord and cerebral cortex. A progressive increase in IR-Leu-enkephalin in amygdala and hippocampus was observed over the course of kindling. These increases remained until 21 days after rats were fully kindled (at least 10 generalized seizures). We observed increased and decreased concentration of each peptide in different regions. We discussed the regional and the differential effects of each peptide. The increased concentrations in limbic structures were associated with the amygdaloid increased excitability through the kindling process. We suggest that the decreases in concentrations are related with structures involved in the output behavior manifestations produced by kindling stimulation.
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PMID:Regional brain IR-Met-, IR-Leu-enkephalin concentrations during progress and full electrical amygdaloid kindling. 272 Mar 96

Seven L-amino acids (Trp, Arg, Lys, Met, Ile, Val, and Phe) partially (28-81%) reversed the inhibitory action of 1 microM gamma-aminobutyric acid (GABA) on t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to rat brain membranes, with EC50 values ranging from 5 to 120 mM. D-Trp, D-Arg, D-Lys, D-Met, D-Val, and D-Phe were approximately equipotent with their L-isomers. Tyramine, phenethylamine, and tryptamine, the decarboxylation products of the aromatic amino acids (Tyr, Phe, and Trp, respectively), reversed the inhibitory action of 1 microM GABA on [35S]TBPS binding more potently than the parent amino acids (EC50 values = 1.5-3.0 mM). Human hereditary amino acidemias involving Arg, Lys, Ile, Val, and Phe are associated with seizures, and these amino acids and/or their metabolites may block GABA-A receptors. Five other L-amino acids (ornithine, His, Glu, Pro, and Ala) as well as Gly and beta-Ala inhibited [35S]TBPS binding with IC50 values ranging from 0.1 to 37 mM, and these inhibitions were reversed by the GABA-A receptor blocker R 5135 in all cases. The inhibitory effects of L-ornithine, L-Ala, L-Glu, and L-Pro were stereospecific, because the corresponding D-isomers were considerably less inhibitory. L-His, D-His, and L-Glu gave incomplete (plateau) inhibitions. Human hereditary amino acidemias involving L-ornithine, His, Pro, Gly, and beta-Ala are also associated with seizures, and we speculate that these GABA-mimetic amino acids may desensitize GABA-A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Two groups of amino acids interact with GABA-A receptors coupled to t-[35S]butylbicyclophosphorothionate binding sites: possible involvement with seizures associated with hereditary amino acidemias. 284 55

The purpose of this study was to determine the role that dentate granule cells play in wet dog shakes (WDS), behavioral seizures, and hippocampal cell loss caused by systemic administration of kainic acid (KA). Rats were given bilateral injections of colchicine (COL) into the hippocampal formation to selectively lesion dentate granule cells. Two weeks later, they were injected subcutaneously with KA and were observed for WDS and seizures. Seizures were terminated with pentobarbital 2.5 hr after KA injection, and the rats were killed 48 hr later. The integrity of hippocampal cell populations and projections to the hippocampal formation from entorhinal cortex was assessed with radioimmunoassay and immunostaining for methionine-enkephalin (ME) and dynorphin (DYN) A, as well as with Timm and Nissl staining. Results indicate that COL injections eliminated KA-induced WDS, did not affect the latency to onset of seizures, and potentiated KA-induced cell loss in the CA3 region of hippocampus. COL lesions eliminated ME and DYN immunostaining of granule cells, but not ME immunostaining of entorhinal afferents to the dentate gyrus or Ammon's horn. These findings indicate that granule cells are an essential neuronal link in the expression of KA-induced WDS, but that seizures propagate along other pathways in the limbic system.
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PMID:Dentate granule cells are essential for kainic acid-induced wet dog shakes but not for seizures. 289 98

Mice given intraperitoneal injections of methionine sulfoximine (MSO) (100 mg/kg body weight) showed tonic-clonic seizures 7 to 8 h later. The protein synthesis inhibitors actinomycin D and cycloheximide, when combined with MSO delayed the onset of seizures. Methionine completely abolished the convulsions and metyrapone delayed them for some hours. Twenty-four h after the administration of the convulsant, the activity of the gluconeogenic enzyme, fructose-1, 6-biphosphatase (FBPase), and the glycogen content were determined in different areas of the brain. MSO induced an increase in both FBPase activity and glycogen content. These effects were antagonized by the inhibitors of protein synthesis. Metyrapone partly inhibited MSO-induced increases of FBPase activity and glycogen content whereas methionine completely abolished them. MSO decreased glycogen content in liver but had no effect on blood glucose level 24 h after its administration. These findings suggested that in MSO epileptogenic brain, glycogen accumulation may proceed from an enhanced gluconeogenesis.
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PMID:Glycogen content and fructose-1, 6-biphosphatase activity in methionine sulfoximine epileptogenic mouse brain and liver after protein synthesis inhibition. 299 93


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