Abstracts

Rationale: Recently, we have found that anti-oxidant ability was remarkably decreased in the hippocampus (Hipp) of EL at 10 weeks of age utilizing ESR spectroscopy. In this study, in addition to evaluation of extracellular glutamate concentration, we tried to examine whether the expression of cystine/glutamate exchanger (xCT) and glutamate transporter changes are observed or not in the Hipp of EL.Methods: EL mice and DDY mice were used for the experiments of Exp. I and II at 5, 10 and 20 weeks of age, respectively. Exp. I: During interictal state, dialysate was collected from the ventral Hipp using microdialysis technique, and extracellular concentration of glutamate ([Glu]o) was measure by HPLC-ECD. Exp. II: Hippocampal expression of glutamate transporter and xCT was estimated by western blots.Results: Exp.I: The level of [Glu]o at 10 weeks of age was remarkably higher among the other age of EL mice, while [Glu]o of DDY was not changed following the ages. Exp.II: excitatory amino acid carrier-1(EAAC-1) and xCT of EL mice at 10 weeks of age was decreased rather than that of DDY. GLAST and GLT-1 of EL mice at 5 weeks of age was decreased compared with DDY at the same age. No differences were found between EL and DDY for GLAST and GLT-1 at the other of ages.Conclusions: According to our previous studies, decreased endogenous anti-oxidant ability found at 10 weeks of age might be powerful candidate to explain the ictogenesis. Decreased xCT expression at 10 weeks of age could provide the molecular mechanism to explain the depletion of endogenous anti-oxidant ability of EL mice during ictogenesis. In addition to the depletion of anti-oxidant ability, decreased EAAC-1 at this period could be one of the collapse of molecular action of inhibition. These molecular findings support the elevation of [Glu]o at 10 weeks of age may trigger the ictogenesis. Funding supported by Grant-in-Aid for Scientific Research (C) (2) (18591297) from the Ministry of Education, Science, Sport and Culture, Japan (to Y.U.)