Neurogenesis in adolescent brain is potently inhibited by ethanol.
Adolescence is a period of progressive changes in brain that likely contribute to the maturation of behavior. Human adolescents consume large amounts of ethanol. To investigate the effects of ethanol on adolescent neural progenitor cells, male rats (35-40 days old) were treated with an acute dose of ethanol (1.0, 2.5 or 5.0 g/kg, i.g.) or vehicle that resulted in peak blood levels of 33, 72, and 131 mg/dl, respectively. Bromodeoxyuridine (300 mg/kg i.p.) was administered to label dividing cells and rats were killed at 5 h to assess proliferation or at 28 days to assess cell survival and differentiation. After 5 h, bromodeoxyuridine-immunoreactivity was reduced by 63, 97 and 99% in the rostral migratory stream and 34, 71 and 99% in the subventricular zone by 1.0, 2.5 and 5.0 g/kg of ethanol respectively. In the dentate gyrus, ethanol reduced bromodeoxyuridine-immunoreactivity by 29, 40, and 78% at the three doses respectively. The density of doublecortin immunoreactivity was decreased after 3 days and the number of bromodeoxyuridine+ cells remained decreased at 28 days when most hippocampal bromodeoxyuridine+ cells coexpressed neuronal nuclei, a neuronal marker. These studies indicate that the adolescent brain is very sensitive to acute ethanol inhibition of neurogenesis.
Crews
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Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, 1021 Thurston Bowles Building, CB 7178, 27599-7178, USA. ftcrews@med.unc.edu
Mdzinarishvili
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Kim
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Nixon
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D000375:Aging / Q000187:drug effects / Q000502:physiology; D020268:Alcohol-Induced Disorders, Nervous System / Q000473:pathology / Q000503:physiopathology*; D000437:Alcoholism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000089662:Doublecortin Protein; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000009:adverse effects*; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000502:physiology*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology
D002492:Central Nervous System Depressants; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D000431:Ethanol