ELECTROCONVULSIVE SEIZURE INCREASES THE EXPRESSION OF CREM (CYCLIC-AMP RESPONSE ELEMENT MODULATOR) AND ICER (INDUCIBLE CYCLIC-AMP EARLY REPRESSOR) IN RAT-BRAIN

Rapid expression of ICER (inducible cyclic AMP early repressor), an in ducible member of the CREM (cyclic AMP response element modulator) fam ily of transcription factors, has been reported in neuroendocrine tiss ues and cell lines, but not in brain. In the present study, we demonst rate that acute electroconvulsive seizure (ECS) increases the expressi on of ICER in several rat brain regions. RNase protection analysis dem onstrated that 1-2 h after administration of ECS, levels of mRNA for I CER and a splice variant, ICER gamma, were significantly increased in hippocampus, frontal cortex, and cerebellum. It is surprising that ECS also increased levels of mRNA for several CREM isoforms that previous studies have reported were not rapidly inducible. In situ hybridizati on analysis confirmed these findings and demonstrated that ECS inducti on of ICER was most obvious in the dentate gyrus granule cell layer of hippocampus and deep layers of cerebral cortex. Induction of ICER and CREM was accompanied by increased expression of two small CRE-binding complexes. Gel supershift analysis with CREM/ICER antisera confirmed that the inducible CRE-binding complexes contain CREM/ICER. Induction of CREM and ICER may contribute to negative feedback regulation of gen e transcription that is increased by acute seizure and activation of C REB (cyclic AMP response element-binding protein).