백서 뇌에서 전기경련충격에 의한 AP-1 결합 활성도의 변화

Changes of AP-1 Binding Activities in Rat Brain by Electroconvulsive Shock

Objectives：ECS could have therapeutic effects on psychiatric illnesses by inducing IEGs, which in turn regulates expression of their target genes. We observed AP-1 binding activity and identified AP-1 binding proteins in NMDAR1, late response gene of IEGs, which considered as the candidate gene for schizophrenia. Methods：By gel shift assay and supershift assay, we observed binding activities and AP-1 binding proteins in NMDAR1. Because IEGs are induced rapidly but transiently by external stimuli, there is a possibility that the expression of IEGs is negatively feedbacked by their own products via their AP-1 binding sites. For that purpose, we also observed AP-1 binding activity of c-fos and c-jun via gel shift and supershift assay. Results：ECS increased AP-1 binding activities of NMDAR1 gene, contributed by c-Fos and its related proteins. Peak of the increased binding was 60 minutes in both hippocampus and cerebellum. Though expression of c-Fos and c-Jun were increased by ECS, there were no changes in AP-1 binding activities after ECS. AP-1 sites of IEGs were binded by CREB, regardless of ECS. Conclusion：There is a possibility that ECS induced IEG expression, and then incresed expression of NMDR1 by binding of expressed IEGs to the AP-1 site of NMDAR1. ECS did not increase AP-1 binding activities of IEGs. This suggests that the regulation of IEGs’ expression can not be influenced mainly by AP-1 site.