Journal
CURRENT MEDICINAL CHEMISTRY
Volume 16, Issue 7, Pages 841-853Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/092986709787549316
Keywords
Epilepsy; methionine sulfoximine; chemically-induced epilepsy; glycogen; astrocytes; glycogenesis; gluconeogenesis
Funding
- Ministere de l'Education Nationale de la Recherche et de l'Enseignement Superieur
- Centre National de la Recherche Scientifique
- Region Centre
- La ligue contre le Cancer via its regional council
- Conseil General du Loiret
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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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