Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein.
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.
Nakagawa
Shin
S
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
Kim
Ji-Eun
JE
Lee
Rena
R
Malberg
Jessica E
JE
Chen
Jingshan
J
Steffen
Cathy
C
Zhang
Ya-Jun
YJ
Nestler
Eric J
EJ
Duman
Ronald S
RS
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
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