Chronic Nicotine Administration Impairs Activation of Cyclic AMP-Response Element Binding Protein and Survival of Newborn Cells in the Dentate Gyrus

    Authors

    Z. L. Wei; C. Belal; W. H. Tu; S. Chigurupati; N. J. Ameli; Y. M. Lu;S. L. Chan

    Comments

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    Abbreviated Journal Title

    Stem Cells Dev.

    Keywords

    ADULT NEUROGENESIS; HIPPOCAMPAL-NEURONS; ALZHEIMERS-DISEASE; BDNF; EXPRESSION; SPATIAL MEMORY; NEURAL STEM; CREB; RECEPTOR; CAMP; PROLIFERATION; Cell & Tissue Engineering; Hematology; Medicine, Research &; Experimental; Transplantation

    Abstract

    Chronic intake of nicotine can impair hippocampal plasticity, but the underlying mechanism is poorly understood. Here, we demonstrate that chronic nicotine administration in adult rats inactivates the cyclic AMP-response element binding protein (CREB), a transcription factor that regulates neurogenesis and other plasticity-related processes necessary for learning and memory. Consequently, we showed that impaired CREB signaling is associated with a significant decline in the production of new neurons in the dentate gyrus. Combining retrovirus labeling with gene expression approaches, we found that chronic nicotine administration reduces the number of adult-generated granule neurons by decreasing the survival of newborn cells but not the proliferation of progenitor cells. Additionally, we found that retroviral-mediated expression of a constitutively active CREB in the dentate gyrus rescues survival of newborn cells and reverses the nicotine-induced decline in the number of mature granule neurons. Prolonged nicotine exposure also compromises CREB activation and reduces the viability of progenitor cells in vitro, thereby suggesting that nicotine may exert its adverse effects directly on immature cells in vivo. Taken together, these data demonstrate that inhibition of CREB activation is responsible for the nicotine-induced impairment of hippocampal plasticity.

    Journal Title

    Stem Cells and Development

    Volume

    21

    Issue/Number

    3

    Publication Date

    1-1-2012

    Document Type

    Article

    Language

    English

    First Page

    411

    Last Page

    422

    WOS Identifier

    WOS:000300266900008

    ISSN

    1547-3287

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