Correlation between brain glycogen and convulsive state in mice submitted to methionine sulfoximine

It is now well established that in epileptic patients, hypometabolic foci a ppear during interictal periods. The meaning and the mechanism of such an h ypometabolism are as yet unclear. The aim of the present investigation was to look for a putative relationship between glucose metabolism in the brain and the genesis of seizures in mice using administration of the convulsant , methionine sulfoximine. Besides its epileptic action, methionine sulfoxim ine is a powerful glycogenic agent. We analyzed the epileptogenic and glyco genic effects of methionine sulfoximine in two inbred mouse strains with di fferent susceptibility towards the convulsant. CBA/J mice displayed high re sponse to methionine sulfoximine. The tonic convulsions appeared 5-6 h afte r MSO administration, without brain glycogen content variations during the preconvulsive period. These mice died of status epilepticus during the firs t seizure(s). Conversely, C57BL/6J mice displayed low response to MSG. The tonic and clonic seizures appeared 8 to 14 h after MSO administration with only 2% mortality. The seizures were preceded by an increase in brain glyco gen content during the preconvulsive period. Moreover, during seizures, C57 BL/6J mice were able to mobilize this accumulated brain glycogen, that retu rned to high value after seizures. The epileptic and glycogenic responses o f the parental strains were also observed in mice of the F2 generation. The F2 mice that convulsed early (16%) did not utilize their small increase in brain glycogen content, and resembled CBA/J mice; while the F2 mice that s eized tardily (24%) increased their brain glycogen content before convulsio n, utilized it during convulsions, and resembled C57BL/6J mice. Sixty perce nt of the F2 mice presented an intermediate pattern in epileptogenic respon ses to the convulsant. These data suggest a possible genetic link between t he two MSO effects, epileptiform seizures and increase in brain glycogen co ntent. The increase in brain glycogen content and the capability of its mob ilization during seizures could delay the seizure's onset and could be cons idered a "resistance factor" against the seizures. (C) 2000 Elsevier Scienc e Inc. All rights reserved.