演題番号 : P3-o02
小島 俊男 / Toshio Kojima:1,2 植田 勇人 / Yuto Ueda:3 北本 綾 / Aya Kitamoto:2 佐藤 明 / Akira Sato:2 足立 直樹 / Naoki Adati:2 L. James Willmore:4
1:浜松医大・機器セ / Res Equip Ctr, Hamamatsu Univ Sch Med, Hamamatsu 2:理研・メタシステム / Metasys T, RIKEN, Yokohama 3:宮崎大・医・精神 / Sect Psych, Univ Miyazaki, Miyazaki 4:Dept Neuro Pharmaco Physiol, Saint Louis Univ, St. Louis, USA
The molecular mechanism underlying the pathology of secondary epileptic generalization remains unknown. In the present study, we performed comprehensive gene expression and gene network analyses using a DNA microarray to elucidate the molecular events responsible for the secondary epileptic generalization. We used an experimental posttraumatic epilepsy model of amygdalar focal FeCl3 injected rats, and compared gene expression profiles in hippocampi at partial seizure stage (less than stage 3 by Racine's convulsion-scale) and at secondary generalized seizure stage (stage 4 or 5). At partial seizure stage, upregulations of a group of genes related to the lipid metabolisms including phospholipase A2 and downregulations of a group of genes related to the glutathione peroxidase dependent defense system against oxidative stress were observed, which have been reported to be caused by brain injury and seizures in previous studies. These differential regulations of genes related to the lipid metabolism and the antioxidant defense system at the stage would be connected with seizure propagation, which would finally lead to the secondary generalization. In contrast to these changes at partial seizure, defensive system by glutathione and glutathione peroxidase was decreased at the stage of generalized seizure. These results would lead to uncover the molecular mechanisms underlying epileptogenesis, which has not fully been understood.