Glutathione levels in specific brain regions of genetically epileptic (tg/tg) mice.

The tottering (tg/tg) mouse is a genetic model of human generalized epilepsy; these mice exhibit spontaneous absence seizures accompanied by bilaterally synchronous spike-wave discharges (6). The mechanism(s) for seizure activity are unknown in these mice. Several recent studies have suggested that membrane lipid peroxidation may be causally involved in some forms of experimentally induced epilepsies (18). Since reduced glutathione (GSH) is the most important free radical scavenging compound in vivo that can prevent membrane lipid peroxidation, the objective of this study was to investigate GSH concentrations in specific central nervous system regions of genetically epileptic, tg/tg, mice as compared to age-matched controls. Three brain regions, cerebellum, hippocampus, and occipital cortex, were dissected, weighed and the concentrations of reduced and oxidized glutathione (GSH and GSSG, respectively) were measured in each of these tissues. GSH content was significantly lower in the occipital cortex of tg/tg mice compared to controls; no differences were observed in the other two brain regions examined. Total GSH content (GSH plus 2 x GSSG) paralleled GSH concentration differences. GSSG content from tg/tg mice was lower in the hippocampus and occipital cortex, compared to controls. This is the first report of an association between decreased central nervous system glutathione concentrations and seizure activity in animals exhibiting generalized seizures.