Distinct cell proliferation events during abstinence after alcohol dependence: microglia proliferation precedes neurogenesis.
Excessive alcohol intake characteristic of Alcohol Use Disorders (AUDs) produces neurodegeneration that may recover with abstinence. The mechanism of regeneration is unclear, however neurogenesis from neural stem/progenitor cells is a feasible mechanism of structural plasticity. Therefore, a timecourse of cell proliferation was examined in a rat model of an AUD and showed a striking burst in cell proliferation at 2 days of abstinence preceding the previously reported neurogenic proliferation at 7 days. New cells at 2 days, assessed by bromo-deoxy-uridine incorporation and endogenous markers, were observed throughout hippocampus and cortex. Although the majority of these new cells did not become neurons, neurogenesis was not altered at this specific time point. These new cells expressed a microglia-specific marker, Iba-1, and survived at least 2 months. This first report of microglia proliferation in a model of an AUD suggests that microgliosis could contribute to volume recovery in non-neurogenic regions during abstinence.
Nixon
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Department of Pharmaceutical Sciences, The University of Kentucky, College of Pharmacy, 725 Rose Street, Lexington, KY 40536-0082, USA.
Kim
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Potts
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Crews
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D020268:Alcohol-Induced Disorders, Nervous System / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001973:Bromodeoxyuridine; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D005911:Gliosis / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008840:Microfilament Proteins; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
C100745:Aif1 protein, rat; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D001973:Bromodeoxyuridine