Alterations of cAMP response element-binding activity in the aged rat brain in response to administration of rolipram, a cAMP-specific phosphodiesterase inhibitor

Masato Asanuma, Sakiko Nishibayashi, Emi Iwata, Yoichi Kondo, Tohru Nakanishi, Marvin Gómez Vargas, Norio Ogawa

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Transcription factor, cAMP response element-binding protein (CREB), which is phosphorylated by cAMP-dependent kinase via an increase in cAMP, and regulates gene transcription by binding to the cAMP response element (CRE) on target genes. We examined age-dependent alterations in the DNA-binding activity of CREB in rat brain regions, and the effects of rolipram, a cAMP-specific phosphodiesterase (PDE) inhibitor on the CRE-binding activity by electrophoretic mobility-shift assay (EMSA). A marked age-dependent decrease in the CRE-binding activity was shown in all brain regions examined, especially in the basal forebrain, the striatum and the hippocampus. Furthermore, CRE-binding activities in the basal forebrain of both young-adult and aged rats significantly increased 2 h after rolipram administration (1 mg/kg, i.p.), and the rolipram treatment recovered the decreased CRE-binding activity in the aged rats. The saturation experiment in EMSA also revealed that rolipram reversed the decrease in the maximum CRE-bindings in the basal forebrain with aging. Since the 5' upstream region of the rat choline acetyltransferase (ChAT) gene contains CRE, and ChAT-positive neurons in the basal forebrain project to the frontal cortex and the hippocampus, rolipram may exert its previously reported ameliorating effect on the age-related reductions of ChAT activities in the frontal cortex and the hippocampus by phosphorylating CREB in the basal forebrain with activation of cAMP-dependent protein kinase via inhibition of PDE.

Original languageEnglish
Pages (from-to)210-215
Number of pages6
JournalMolecular Brain Research
Volume41
Issue number1-2
DOIs
Publication statusPublished - Sep 5 1996

Keywords

  • Aging
  • Brain
  • Phosphodiesterase inhibitor
  • Rolipram
  • Transcription factor
  • cAMP response element

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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