Ethanol-induced neurotoxicity is counterbalanced by increased cell proliferation in mouse dentate gyrus.
Chronic ethanol abuse leads to degenerative changes in the hippocampus, which may result in subsequent cognitive impairment. Since the hippocampus retains the ability to produce neurons through adulthood, in the present study we examined if ethanol-induced neuronal loss could be counterbalanced by cell proliferation in mouse dentate gyrus (DG). A total of 14 days of ethanol administration resulted in marked increase in cells positive for TdT-mediated dUTP nick-end labeling in all hippocampal regions studied, indicating that neurons die throughout the hippocampus by apoptotic mechanism. However, cresyl violet staining revealed approximately 20% neuronal loss following ethanol administration in CA1 and CA2 fields (P<0.01 and P<0.05, respectively), but not in DG. At the same time ethanol caused 2-fold increase in the number of proliferating cells in subgranular zone of DG. Thus, long-term ethanol intoxication causes permanent damage to CA1 and CA2, but not to DG which can be counterbalanced by ongoing neurogenesis.
Pawlak
Robert
R
Department of Pharmacodynamics, Medical Academy of Bialystok, Mickiewicza 2C, 15-230 Bialystok, Poland.
Skrzypiec
Anna
A
Sulkowski
Stanislaw
S
Buczko
Wlodzimierz
W
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity*; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology*
D002492:Central Nervous System Depressants; D000431:Ethanol