title: Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein.
abstract: The cAMP cascade, including the cAMP response element-binding protein (CREB), is known to play an important role in neuronal survival and plasticity. Here the influence of this cascade on neurogenesis in adult hippocampus was determined. Activation of the cAMP cascade by administration of rolipram, an inhibitor of cAMP breakdown, increased the proliferation of newborn cells in adult mouse hippocampus. In addition, rolipram induction of cell proliferation resulted in mature granule cells that express neuronal-specific markers. Increased cell proliferation is accompanied by activation of CREB phosphorylation in dentate gyrus granule cells, suggesting a role for this transcription factor. This possibility is supported by studies demonstrating that cell proliferation is decreased in conditional transgenic mice that express a dominant negative mutant of CREB in hippocampus. The results suggest that the cAMP-CREB cascade could contribute to the actions of neurotransmitters and neurotrophic factors on adult neurogenesis.
authors.affiliation: Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
authors.forename: Shin
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Rena
authors.initials: R
authors.lastname: Lee
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Malberg
authors.forename: Jingshan
authors.initials: J
authors.lastname: Chen
authors.forename: Cathy
authors.initials: C
authors.lastname: Steffen
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Duman
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D019943:Amino Acid Substitution; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001973:Bromodeoxyuridine; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005799:Genes, Dominant; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D020889:Rolipram / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000943:Antigens, Differentiation; D017362:Cyclic AMP Response Element-Binding Protein; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D001973:Bromodeoxyuridine; D020889:Rolipram