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

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

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

Rats and mice were submitted either to the convulsant methionine sulfoximine (MSO) alone or to MSO combined with actinomycin D or methionine respectively. Twenty-four hours after the intraperitoneal administration of these compounds, the animals were killed and tissue samples were prepared for electron microscopy. Methionine sulfoximine induced 'grand mal' type seizures which were abolished by methionine. In saline controls, glycogen was as beta particles located in the cytoplasm of astrocytes, i.e. in perikarya and processes. Liver glycogen was as perinuclear masses of alpha and beta particles or as alpha particles scattered in all the cytoplasm. When the rodents were treated with MSO, glycogen was as alpha and beta particles which invaded all areas of the astrocyte cytoplasm, this increase being tremendous in perivascular end feet. Actinomycin D slowed down the accumulation of glycogen particles while methionine completely abolished it. In any case, glycogen particles were confined to the astrocytes and were never seen in other types of cells. In liver, MSO induced an important decrease or a complete disappearance of glycogen particles. When the convulsant was combined with actinomycin D or with methionine, the figures looked like those of controls. These results have been discussed in relation to the mechanism of glycogenesis in central nervous system of rodents submitted to MSO.
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PMID:Glycogen particles in methionine sulfoximine epileptogenic rodent brain and liver after the administration of methionine and actinomycin D. 402 58

Methionine sulfoximine induces epileptiform convulsions in rats. A possible involvement of acetylcholine in the onset of convulsions was investigated. A subconvulsive dose of methionine sulfoximine increased the brain acetylcholine concentration. After administration of a convulsive dose, atropine neither prevented the onset of the seizures nor prevented the increase in acetylcholine concentration. Physostigmine enhanced the increase in acetylcholine level but did not modify the time course nor the intensity of the convulsions. L-DOPA suppressed the seizures without inhibiting the increase in acetylcholine level. The choline content decreased after the convulsant dose. The increase in acetylcholine content is therefore not the unique cause of the seizures, which could result from the reduction of striatal inhibition due to a decrease in dopamine level induced by methionine sulfoximine.
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PMID:Methionine sulfoximine increases acetylcholine level in the rat brain: no relation with epileptogenesis. 858 Apr 33

Seizures are the result of a sudden and temporary synchronization of neuronal activity, the reason for which is not clearly understood. Astrocytes participate in the control of neurotransmitter storage and neurotransmission efficacy. They provide fuel to neurons, which need a high level of energy to sustain normal and pathological neuronal activities, such as during epilepsy. Various genetic or induced animal models have been developed and used to study epileptogenic mechanisms. Methionine sulfoximine induces both seizures and the accumulation of brain glycogen, which might be considered as a putative energy store to neurons in various animals. Animals subjected to methionine sulfoximine develop seizures similar to the most striking form of human epilepsy, with a long pre-convulsive period of several hours, a long convulsive period during up to 48 hours and a post convulsive period during which they recover normal behavior. The accumulation of brain glycogen has been demonstrated in both the cortex and cerebellum as early as the pre-convulsive period, indicating that this accumulation is not a consequence of seizures. The accumulation results from an activation of gluconeogenesis specifically localized to astrocytes, both in vivo and in vitro. Both seizures and brain glycogen accumulation vary when using different inbred strains of mice. C57BL/6J is the most "resistant" strain to methionine sulfoximine, while CBA/J is the most "sensitive" one. The present review describes the data obtained on methionine sulfoximine dependent seizures and brain glycogen in the light of neurotransmission, highlighting the relevance of brain glycogen content in epilepsies.
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PMID:Epilepsy, regulation of brain energy metabolism and neurotransmission. 1927 97

The prevalence of depression and suicide is increased in patients with mesial temporal lobe epilepsy (MTLE); however, the underlying mechanism remains unknown. Anhedonia, a core symptom of depression that is predictive of suicide, is common in patients with MTLE. Glutamine synthetase, an astrocytic enzyme that metabolizes glutamate and ammonia to glutamine, is reduced in the amygdala in patients with epilepsy and depression and in suicide victims. Here, we sought to develop a novel model of anhedonia in MTLE by testing the hypothesis that deficiency in glutamine synthetase in the central nucleus of the amygdala (CeA) leads to epilepsy and comorbid anhedonia. Nineteen male Sprague-Dawley rats were implanted with an osmotic pump infusing either the glutamine synthetase inhibitor methionine sulfoximine [MSO (n=12)] or phosphate buffered saline [PBS (n=7)] into the right CeA. Seizure activity was monitored by video-intracranial electroencephalogram (EEG) recordings for 21days after the onset of MSO infusion. Sucrose preference, a measure of anhedonia, was assessed after 21days. Methionine sulfoximine-infused rats exhibited recurrent seizures during the monitoring period and showed decreased sucrose preference over days when compared with PBS-infused rats (p<0.01). Water consumption did not differ between the PBS-treated group and the MSO-treated group. Neurons were lost in the CeA, but not the medial amygdala, lateral amygdala, basolateral amygdala, or the hilus of the dentate gyrus, in the MSO-treated rats. The results suggest that decreased glutamine synthetase activity in the CeA is a possible common cause of anhedonia and seizures in TLE. We propose that the MSO CeA model can be used for mechanistic studies that will lead to the development and testing of novel drugs to prevent seizures, depression, and suicide in patients with TLE.
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PMID:Inhibition of glutamine synthetase in the central nucleus of the amygdala induces anhedonic behavior and recurrent seizures in a rat model of mesial temporal lobe epilepsy. 2626 37