Binge ethanol exposure in adult rats causes necrotic cell death.
BACKGROUND
Although alcoholics show neurodegeneration after decades of drinking, recent studies with an animal model of binge drinking have found corticolimbic damage after as few as four days. Neurodegeneration can occur through apoptotic or necrotic mechanisms. The goal of this research is to characterize the time course of binge ethanol-induced neurodegeneration and to identify apoptotic or necrotic characteristics of this neurodegeneration.


METHODS
Histologic methods (e.g., amino cupric silver staining, Fluoro-Jade B, hematoxylin and eosin, transmission electron microscopy) were used to quantify the time course of degeneration and to characterize the ultrastructural changes that occur with binge ethanol-induced neurodegeneration.


RESULTS
After 2 days of binge ethanol, significant damage was evident in the olfactory bulb. After 4 days of binge ethanol, there was significant damage in the agranular insular cortex, anterior piriform cortex, perirhinal cortex, lateral entorhinal cortex, and the temporal dentate gyrus. Ultrastructural examination revealed shrunken soma, vacuolated cytoplasm, pyknotic nucleus, and irregularly clumped chromatin consistent with dark cell degeneration, a form of necrotic neuronal death.


CONCLUSIONS
Binge drinking causes necrotic neurodegeneration after 2 days of exposure and increased damage after 4 days but does not increase during withdrawal. These studies indicate that binge drinking induced neurodegeneration is necrotic and occurs during ethanol intoxication and not as a result of ethanol withdrawal.
Obernier
J A
JA
Bowles Center for Alcohol Studies, Department of Pharmacology, University of North Carolina at Chapel Hill, 27599-7178, USA.
Bouldin
T W
TW
Crews
F T
FT
D000375:Aging / Q000187:drug effects* / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000648:ultrastructure; D016923:Cell Death / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D018891:Dentate Gyrus / Q000473:pathology / Q000648:ultrastructure; D004801:Eosine Yellowish-(YS); D000431:Ethanol / Q000633:toxicity*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006416:Hematoxylin; D020287:In Situ Nick-End Labeling; D008297:Male; D009336:Necrosis; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000473:pathology; D009830:Olfactory Bulb / Q000187:drug effects / Q000473:pathology; D009930:Organic Chemicals; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling
D002492:Central Nervous System Depressants; D005452:Fluoresceins; D005456:Fluorescent Dyes; D009930:Organic Chemicals; C435731:fluoro jade; D000431:Ethanol; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin