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Publication : cAMP response element-binding protein regulates differentiation and survival of newborn neurons in the olfactory bulb.

First Author  Giachino C Year  2005
Journal  J Neurosci Volume  25
Issue  44 Pages  10105-18
PubMed ID  16267218 Mgi Jnum  J:102357
Mgi Id  MGI:3607407 Doi  10.1523/JNEUROSCI.3512-05.2005
Citation  Giachino C, et al. (2005) cAMP response element-binding protein regulates differentiation and survival of newborn neurons in the olfactory bulb. J Neurosci 25(44):10105-18
abstractText  The transcription factor cAMP response element-binding protein (CREB) is involved in multiple aspects of neuronal development and plasticity. Here, we demonstrate that CREB regulates specific phases of adult neurogenesis in the subventricular zone/olfactory bulb (SVZ/OB) system. Combining immunohistochemistry with bromodeoxyuridine treatments, cell tracer injections, cell transplants, and quantitative analyses, we show that although CREB is expressed by the SVZ neuroblasts throughout the neurogenic process, its phosphorylation is transient and parallels neuronal differentiation, increasing during the late phase of tangential migration and decreasing after dendrite elongation and spine formation. In vitro, inhibition of CREB function impairs morphological differentiation of SVZ-derived neuroblasts. Transgenic mice lacking CREB, in a null CREM genetic background, show reduced survival of newborn neurons in the OB. This finding is further supported by peripheral afferent denervation experiments resulting in downregulation of CREB phosphorylation in neuroblasts, the survival of which appears heavily impaired. Together, these findings provide evidence that CREB regulates differentiation and survival of newborn neurons in the OB.
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