Cerebral methylations in epileptogenesis

This chapter deals with the neurochemical consequences of the administration of the chemical convulsant agent L-methionine-dl-sulfoximine (MSO) on the brain of rodents. The principal notion is that this convulsant agent differs qualitatively from most quick-acting and predominantly lethal convulsant agents, commonly used in laboratory studies in epilepsy modeling because it has a preconvulsant latency period of several hours and also because it need not be fatal to the animals receiving it if they are properly managed during the preconvulsant period and following the first seizure attack. The historical profile of MSO as a useful and unique laboratory tool for neurochemical and molecular studies is briefly recounted, and the point is made that MSO is a close derivative of the amino acid L-methionine, which is used by each and every brain cell as a protein building block and as a precursor of the universal cellular methyl donor molecule, S-adenosyl-L-methionine. The importance of methylations, a set of reactions which consist in the transfer of the methyl group of S-adenosyl-L-methionine to several dozens of endogenous methyl acceptor molecules, small and large, is stressed and reviewed both historically and as this process relates to MSO epileptogenesis. The multiple effects of MSO on the methylation of small MW compounds, histamine being the working example, are reviewed. The involvement of phospholipid, nucleic acid, and protein methylations, all apparent targets of MSO action, in that they respond to the MSO challenge by a significant rate increase is elucidated. Finally, the effects of MSO at the functional level of brain receptor action are presented.(ABSTRACT TRUNCATED AT 250 WORDS)