Exercise neuroprotection in a rat model of binge alcohol consumption



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Alcoholism: Clinical and Experimental Research


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.



Alcoholism, Neurodegeneration, Dentate gyrus, Adult neurogenesis, Ethanol


Copyright 2010 Alcoholism: Clinical and Experimental Research. This is a post-print version of a published paper that is available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.2009.01105.x/full. Recommended citation: Leasure, J. Leigh and Kimberly Nixon. "Exercise Neuroprotection in a Rat Model of Binge Alcohol Consumption." Alcoholism: Clinical and Experimental Research 34, no. 3 (2010): 404-414. doi: 10.1111/j.1530-0277.2009.01105.x. This item has been deposited in accordance with publisher copyright and licensing terms and with the author's permission.