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The Journal of Neuroscience, May 1, 2002, 22(9):3673-3682
Regulation of Neurogenesis in Adult Mouse Hippocampus by cAMP and the cAMP Response Element-Binding Protein
Shin Nakagawa, Ji-Eun Kim, Rena Lee, Jessica E. Malberg, Jingshan Chen, Cathy Steffen, Ya-Jun Zhang, Eric J. Nestler, and Ronald S. Duman Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut 06508
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.
Key words: rolipram; phosphodiesterase; transgenic mice; phosphorylation; proliferation; granule cell; transcription factor
Copyright © 2002 Society for Neuroscience 0270-6474/02/2293673-10$05.00/0
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