Selective impairment of hippocampal neurogenesis by chronic alcoholism: protective effects of an antioxidant.
A major pathogenic mechanism of chronic alcoholism involves oxidative burden to liver and other cell types. We show that adult neurogenesis within the dentate gyrus of the hippocampus is selectively impaired in a rat model of alcoholism, and that it can be completely prevented by the antioxidant ebselen. Rats fed for 6 weeks with a liquid diet containing moderate doses of ethanol had a 66.3% decrease in the number of new neurons and a 227-279% increase in cell death in the dentate gyrus as compared with paired controls. Neurogenesis within the olfactory bulb was not affected by alcohol. Our studies indicate that alcohol abuse, even for a short duration, results in the death of newly formed neurons within the adult brain and that the underlying mechanism is related to oxidative or nitrosative stress. Moreover, these findings suggest that the impaired neurogenesis may be a mechanism mediating cognitive deficits observed in alcoholism.
Herrera
Daniel G
DG
Department of Psychiatry, Weill Medical College of Cornell University, New York, NY 10021, USA. dah2007@med.cornell.edu
Yague
Almudena G
AG
Johnsen-Soriano
Siv
S
Bosch-Morell
Francisco
F
Collado-Morente
Lucia
L
Muriach
Maria
M
Romero
Francisco J
FJ
Garcia-Verdugo
J Manuel
JM
D000437:Alcoholism; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000431:Ethanol / Q000009:adverse effects*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D054833:Isoindoles; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009584:Nitrogen / Q000378:metabolism; D009830:Olfactory Bulb / Q000187:drug effects; D016566:Organoselenium Compounds / Q000494:pharmacology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000963:Antimetabolites; D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; D000431:Ethanol; C042986:ebselen; D001973:Bromodeoxyuridine; D009584:Nitrogen