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Electroconvulsive Seizure Increases the Expression of CREM (Cyclic AMP Response Element Modulator) and ICER (Inducible Cyclic AMP Early Repressor) in Rat Brain

Authors

  • Laura Rydelek Fitzgerald,

    1. Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, Connecticut, U.S.A.
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  • Vidita A. Vaidya,

    1. Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, Connecticut, U.S.A.
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  • Rosemarie Z. Terwilliger,

    1. Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, Connecticut, U.S.A.
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  • Ronald S. Duman

    Corresponding author
    1. Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, Connecticut, U.S.A.
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Address correspondence and reprint requests to Dr. R. S. Duman at Connecticut Mental Health Center, 34 Park St., New Haven, CT 06508, U.S.A.

Abstract

Abstract: Rapid expression of ICER (inducible cyclic AMP early repressor), an inducible member of the CREM (cyclic AMP response element modulator) family of transcription factors, has been reported in neuroendocrine tissues and cell lines, but not in brain. In the present study, we demonstrate that acute electroconvulsive seizure (ECS) increases the expression of ICER in several rat brain regions. RNase protection analysis demonstrated that 1–2 h after administration of ECS, levels of mRNA for ICER and a splice variant, ICERγ, 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 hybridization analysis confirmed these findings and demonstrated that ECS induction 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 gene transcription that is increased by acute seizure and activation of CREB (cyclic AMP response element-binding protein).

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