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.