백서 뇌에서 전기경련충격에 의한 AP-1 결합 활성도의 변화

Abstract

Objectives ; ECS could have therapeutic effects on psychiatric illnesses by inducing IEGs, which in turn regulate 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 candidate gene for schizophrenia.Methods ; By gel shift assay and supershift assay, we observed binding activities and AP-1 binding protiens in NMDAR1. Because IEGs are induced rapidly but transiently by external stimuli, there might be a possibility that 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 change 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. These suggest that regulation of IEGs' expression should not influenced mainly by AP-1 site. Key words; ECS(electroconvulsive shock), IEG(immediate early gene), AP-1, NMDAR1(N-methyl-D-aspartate receptor)