TY - JOUR T1 - Localization of Phosphorylated cAMP Response Element-Binding Protein in Immature Neurons of Adult Hippocampus JF - The Journal of Neuroscience JO - J. Neurosci. SP - 9868 LP - 9876 DO - 10.1523/JNEUROSCI.22-22-09868.2002 VL - 22 IS - 22 AU - Shin Nakagawa AU - Ji-Eun Kim AU - Rena Lee AU - Jingshan Chen AU - Takashi Fujioka AU - Jessica Malberg AU - Shuichi Tsuji AU - R. S. Duman Y1 - 2002/11/15 UR - http://www.jneurosci.org/content/22/22/9868.abstract N2 - Neurogenesis continues to occur in the adult hippocampus, although many of the newborn cells degenerate 1–2 weeks after birth. The number and survival of newborn cells are regulated by a variety of environmental stimuli, but very little is known about the intracellular signal transduction pathways that control adult neurogenesis. In the present study, we examine the expression of the phosphorylated cAMP response element-binding protein (pCREB) in immature neurons in adult hippocampus and the role of the cAMP cascade in the survival of new neurons. The results demonstrate that virtually all immature neurons, identified by triple immunohistochemistry for bromodeoxyuridine (BrdU) and polysialic acid-neural cell adhesion molecule (PSA-NCAM), are also positive for pCREB. In addition, upregulation of cAMP (via pharmacological inhibition of cAMP breakdown or by antidepressant treatment) increases the survival of BrdU-positive cells. A possible role for pCREB in the regulation of PSA-NCAM, a marker of immature neurons involved in neuronal remodeling and neurite outgrowth, is supported by cell culture studies demonstrating that the cAMP–CREB pathway regulates the expression of a rate-limiting enzyme responsible for the synthesis of PSA-NCAM. These findings indicate that the cAMP–CREB pathway regulates the survival, and possibly the differentiation and function, of newborn neurons. ER -