Abstract
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.
Highlights
Glutamate and -aminobutyric acid (GABA) are the most abundant neurotransmitters in the central nervous system (CNS)
The present review briefly describes human epilepsies and animal models developed to study this disease, as well as data obtained for methionine sulfoximine (MSO) dependent seizures and brain glycogen accumulation
Our two most important concerns are as follows. (i) The existence of a long preconvulsive period during which it is possible to observe changes before the onset of seizures might not be a consequence of crisis. (ii) This model associates an accumulation of brain glycogen with induction of seizures, and allows the analyses of the relationship between seizures and brain glycogen content
Summary
Glutamate and -aminobutyric acid (GABA) are the most abundant neurotransmitters in the central nervous system (CNS). Three classes of ionotropic receptors to glutamate are commonly described, i.e. AMPA (-amino-3hydroxy-5-methylisoazol-4-propionate), NMDA (N-methylD-aspartate) and kainate (kainic acid) receptors. The activation of these receptors induces a K+ ion outward and a Na+ ion inward transport, which in turn induces activation of action potential. The activation of GABAA receptors induces an inward entry of chloride ions, while that of GABAB receptors induces an outflow of K+ ions, both actions lead to an inhibition of neuronal activity. These two complementary and contradictory neurotransmission pathways constitute the targets for most antiepileptic drugs. Brain glycogen will be determined in vivo in the near future, either in animals or in humans, and might be used as a diagnostic tool as well as a therapeutic target
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