Binge ethanol exposure decreases neurogenesis in adult rat hippocampus.
Alcoholism is associated with cognitive deficits and loss of brain mass. Recent studies have indicated that neural progenitor cells proliferate throughout life forming neurons, astrocytes, and oligodendrocytes. The dentate gyrus is one neurogenic region of the adult brain containing neural progenitor cells. To determine if binge ethanol (EtOH) exposure alters neural progenitor cell proliferation and survival, bromodeoxyuridine was administered to adult male rats following an acute or chronic binge exposure paradigm. For an acute binge, rats were gavaged with a 5 g/kg dose of EtOH or vehicle, administered bromodeoxyuridine, and killed either 5 h or 28 days after EtOH treatment. In a 4-day, chronic-binge paradigm, rats were infused with EtOH three times per day (mean dose 9.3 g/kg/day) or isocaloric control diet. Rats were given bromodeoxyuridine once a day for the 4 days of chronic binge treatment, then perfused either immediately following the last dose of EtOH or 28 days later. In both EtOH treatment groups, binge EtOH decreased neural progenitor cell proliferation. Following the chronic four-day binge, neural progenitor cell survival was decreased. These studies are the first to show EtOH inhibition of neural progenitor cell proliferation and survival in the adult, a possible new mechanism underlying alcoholic cognitive dysfunction.
Nixon
Kimberly
K
Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. FTCrew@med.unc.edu
Crews
Fulton T
FT
D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D000431:Ethanol / Q000506:poisoning*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
D000431:Ethanol; D001973:Bromodeoxyuridine