Abstracts

Rationale: EL mouse is an animal model for hereditary multifactorial epilepsy. When the mice receive weekly rapid accelerating movement, seizure emerges at the age of approximately 10 weeks. Seizure develops associated with aging of the mouse, repetition of stimuli and past seizure history. This model is useful for studying mechanisms of epilepsy, epileptogenesis and ictogenesis without any administration of agents. The mechanisms of EL mice seizure development remain unknown. The aim of this study is to test the hypothesis that the EL mice would show hyper-excitability which might cause the seizure susceptibility. Methods: Experiment (Exp.) 1: We observed the changes in intracellular calcium on adult EL and control DDY mice hippocampal slice after oxygen-glucose deprivation (OGD) using calcium imaging with Rhod2-AM. Exp.2: We also performed the same experiments in developing animals (2-8w) to know from when the hyper excitability on CA3 can be seen. Exp.3: We examined the changes in calcium signal under the conditions of calcium removal from the perfusion solution or application of NMDA antagonist D-(-)-2-Amino-5-phosphonopentanoic acid (AP5). Results: Exp.1: In EL mice, the cytosolic calcium on hippocampal CA1 and CA3 was significantly increased after OGD. On the contrary control DDY mice showed increase just on CA1 region. Exp.2: In developing EL mice, calcium increase after OGD was less than the adults evenly in CA1 and CA3. The fluorescent intensity was successively increased in both CA1 and CA3 as it grows. Exp.3: Extracellular calcium free condition and application of AP5 partially decreased the intracellular calcium increase after OGD. Conclusions: These results suggest that enhanced excitability of EL mice on hippocampal CA3 might cause epileptogenesis and ictogenesis. Hyper-excitability occurs gradually as they get older, not after growth and might be related with glutamate NMDA receptor.