Exercise neuroprotection in a rat model of binge alcohol consumption.
BACKGROUND
Excessive alcohol intake produces structural and functional deficits in corticolimbic pathways that are thought to underlie cognitive deficits in the alcohol use disorders (AUDs). Animal models of binge alcohol administration support the direct link of high levels of alcohol consumption and neurotoxicity in the hippocampus and surrounding cortex. In contrast, voluntary wheel running enhances hippocampal neurogenesis and generally promotes the health of neurons.


METHODS
We investigated whether voluntary exercise prior to binge alcohol exposure could protect against alcohol-induced cell loss. Female Long-Evans rats exercised voluntarily for 14 days before undergoing 4 days of binge alcohol consumption. Brains were harvested immediately after the last dose of alcohol and examined for various histological markers of neurodegeneration, including both cell death (FluoroJade B) and cell birth (Ki67) markers.


RESULTS
Rats that exercised prior to binge exposure were significantly less behaviorally intoxicated, which was not a result of enhanced hepatic metabolism. Rats that exercised prior to binge alcohol consumption had reduced loss of dentate gyrus granule cells and fewer FluoroJade B positive cells in the dentate gyrus and associated entorhinal-perirhinal cortex compared to nonexercisers. However, exercise did not protect against cell death in the piriform cortex nor protect against alcohol-induced decreases in cell proliferation, evidenced by a similar alcohol-induced reduction in Ki67 labeled cells between exercise and sedentary rats.


CONCLUSIONS
We conclude that exercise can reduce behavioral sensitivity to ethanol intoxication and protect vulnerable brain areas from alcohol-induced cell death. Exercise neuroprotection of alcohol-induced brain damage has important implications in understanding the neurobiology of the AUDs as well as in developing novel treatment strategies.
Leasure
J Leigh
JL
Department of Psychology, University of Houston, Houston, Texas, USA.
Nixon
Kimberly
K
D000435:Alcoholic Intoxication / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000506:poisoning*; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D000431:Ethanol / Q000506:poisoning*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D010805:Physical Conditioning, Animal; D051381:Rats; D020318:Rats, Long-Evans; D013234:Stem Cells / Q000473:pathology
D002492:Central Nervous System Depressants; D000431:Ethanol