Moderate ethanol consumption increases hippocampal cell proliferation and neurogenesis in the adult mouse.
Alcoholism is a lifelong disease often associated with emotional disturbances and a high risk of relapse even years after detoxification. To explore if cell proliferation in the dentate gyrus of the hippocampus might be important for alcohol-induced brain adaptation, we analysed hippocampal neurogenesis and gliogenesis in adult C57BL/6 mice that consumed moderate levels of ethanol (~6 g/kg.d) in a two-bottle free-choice model during ~10 wk. The mice developed a 53% preference for ethanol vs. water and displayed a blood ethanol concentration of 0.24 per thousand at the time of sacrifice. Bromo-deoxy-uridine (BrdU) was administered in different regimes to analyse proliferation, survival, cell distribution and differentiation of new cells in the dentate gyrus. Moderate ethanol consumption increased the proliferation of cells, which survived and developed a neural phenotype. Ethanol consumption did not induce apoptosis, neither did it change differentiation or the distribution patterns of the newly formed cells. The cell proliferation rate in the dentate gyrus returned to basal levels 3 d after ethanol withdrawal. We conclude that voluntary ethanol intake by mice can change the rate of cell proliferation in the dentate gyrus. These observations add to the emerging picture of dentate gyrus neurogenesis as a highly regulated process. Since there was no increase in apoptosis concomitant with the ethanol-induced increase in neurogenesis, it is possible that the new cells in the dentate gyrus may contribute to the long-lasting changes of brain function after ethanol consumption.
Aberg
Elin
E
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Hofstetter
Christoph P
CP
Olson
Lars
L
Brené
Stefan
S
D000465:Algorithms; D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*
D000963:Antimetabolites; D002492:Central Nervous System Depressants; D000431:Ethanol; D001973:Bromodeoxyuridine