TY - JOUR
T1 - Alterations of cAMP response element-binding activity in the aged rat brain in response to administration of rolipram, a cAMP-specific phosphodiesterase inhibitor
AU - Asanuma, Masato
AU - Nishibayashi, Sakiko
AU - Iwata, Emi
AU - Kondo, Yoichi
AU - Nakanishi, Tohru
AU - Vargas, Marvin Gómez
AU - Ogawa, Norio
PY - 1996/9/5
Y1 - 1996/9/5
N2 - 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.
AB - 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.
KW - Aging
KW - Brain
KW - Phosphodiesterase inhibitor
KW - Rolipram
KW - Transcription factor
KW - cAMP response element
UR - http://www.scopus.com/inward/record.url?scp=0030571016&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030571016&partnerID=8YFLogxK
U2 - 10.1016/0169-328X(96)00098-8
DO - 10.1016/0169-328X(96)00098-8
M3 - Article
C2 - 8883954
AN - SCOPUS:0030571016
VL - 41
SP - 210
EP - 215
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1-2
ER -