Abstracts

Rationale: The aim of this study is to test the hypothesis that EL mice would show hyper-excitability which might cause the seizure susceptibility. Methods: Experiment (Exp.) 1: We observed the changes in intracellular Ca2 on adult EL and control DDY mice hippocampal slice after oxygen-glucose deprivation (OGD) using Ca2 imaging with Rhod2-AM. Exp.2: We also performed the same experiments in developing animals (2-8w). Exp.3: We examined the changes in Ca2 signal under the conditions of calcium free or applying of NMDA antagonist AP5 or AMPA antagonist CNQX. Exp.4: We observed the effect of growing up without acceleration in the developing period. Results: Exp.1: In EL mice, cytosolic Ca2 on CA1 and CA3 was significantly increased after OGD. Control DDY showed increase just on CA1 region. Exp.2: In developing EL mice, Ca2 increase 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 Ca2 free condition, application of AP5 and CNQX partially decreased the intracellular calcium increase after OGD. Exp.4: In the mice without acceleration, the degree of Ca2 increase in CA1 and CA3 was less than accelerated EL mice. Conclusions: These results suggest that enhanced excitability on CA3 in EL mice might cause epileptogenesis. Hyper-excitability occurs gradually as they get older, not after growth and might be related with both glutamate NMDA and AMPA receptors.