Molecular mechanism of DNA fragmentation without cell loss in the epileptic mutant EL mice brain

Address correspondence and reprint requests to: Dr. Y. L. Murashima, Department of Neural Plasticity, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan. Tel :+81-3-3304-5701, Fax:+81-3-3329-8035, E-mail: [email protected] In EL mice, ictogenesis has been established at around 10 weeks of age, whereas epileptogenesis will be established through experience of repetitive seizures during development. It is suggested that an “abnormal neural plasticity” may play a crucial role in the establishment of ictogenesis and epileptogenesis, and therefore, can be a potential target for the development of a new pharmacotherapy to the epilepsy. Recently, antiapototic, proapoptotic factors and neurotrophic factors are suggested to play a key role not only in the cell survival but also in the epileptogenesis. In the brain of EL, DNA fragmentation without cell loss was observed in the parietal cortex and hippocampus which play the key role in the seizure initiation and generalization respectively. To investigate the role of antiapototic, proapoptotic factors and neurotrophic factors in the ictogenesis and epileptogenesis in EL mice brain, developmental changes of these factors are determined.