title: Chronic nicotine administration impairs activation of cyclic AMP-response element binding protein and survival of newborn cells in the dentate gyrus.
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.
authors: Biomedical Sciences Center, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida 32816, USA.
authors: Zelan
authors: Z
authors: Wei
authors: Cherine
authors: C
authors: Belal
authors: Weihong
authors: W
authors: Tu
authors: Srinivasulu
authors: S
authors: Chigurupati
authors: Neema Jason
authors: NJ
authors: Ameli
authors: Youming
authors: Y
authors: Lu
authors: Sic L
authors: SL
authors: Chan
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000008:administration & dosage; D002452:Cell Count; D016923:Cell Death; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage* / Q000009:adverse effects; D051381:Rats; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D003470:Culture Media; D017362:Cyclic AMP Response Element-Binding Protein; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D009538:Nicotine; D001973:Bromodeoxyuridine