RT Journal Article
SR Electronic
T1 Localization of Phosphorylated cAMP Response Element-Binding Protein in Immature Neurons of Adult Hippocampus
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9868
OP 9876
DO 10.1523/JNEUROSCI.22-22-09868.2002
VO 22
IS 22
A1 Shin Nakagawa
A1 Ji-Eun Kim
A1 Rena Lee
A1 Jingshan Chen
A1 Takashi Fujioka
A1 Jessica Malberg
A1 Shuichi Tsuji
A1 R. S. Duman
YR 2002
UL http://www.jneurosci.org/content/22/22/9868.abstract
AB 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.