Abstracts

Rationale: We have recently found that there was DNA fragmentation without cell loss in the hippocampus in EL mice, an epileptic mutant of epilepsy. There was also an abundance of neurotrophic factors expressed during the early developmental stage. In the present study, we used EL mice to examine how altered cyclin and the corresponding cyclin dependent kinase (CDK) family are related to the cell proliferation during development as the seizure predisposition. And further, the Effects of Levetiracetam for the seizure predispositions were examined. Methods: Developmental changes of cyclin family and corresponding CDK family (cyclin D / CDK–4, cyclin E / CDK–2, cyclin A / CDK–2, cyclin A / CDK−1, cyclin B / CDK−1) were examined during cell cycle by Western blotting in the hippocampus of EL mice and their control animal, DDY mice. 160mg/kg Levetiracetam was administered po and mice were sacrificed 19hrs after.Results: As compared with the control DDY mice, EL shows an up–regulation of cell cycle specific Cyclins / CDK’s during early developmental stage suggesting that reentry of cell cycle is promoted prior to the beginning of seizures, possibly due to abundant neurotrophic factors. Levetiracetam abolished these abnormal changes.Conclusions: Cyclins / CDK’s can be activated during early stages of development before exhibiting seizures, suggesting that reentry of cell cycle and cell proliferation in the hippocampus are candidates for the seizure predispositions of EL mice. And Levetiracetam is a very potent reagent to block the seizure predisposition.