How the Alcohol-Damaged Brain Responds to Exercise
Barton, Emily Avalon
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Alcohol use disorders (AUDs) are a public health concern associated with damage to corticolimbic brain regions and cognitive impairments. As the prevalence of AUDs increases, it is necessary to find effective treatments. Exercise is a low-cost adjunctive treatment option that has been investigated. While it provides numerous health and cognitive benefits, the interactive effects of alcohol and exercise on the brain remain largely unexplored. The work presented in this dissertation examines how the timing of exercise following binge alcohol consumption alters exercise-driven plasticity, as well as the interactive effects of binge alcohol and exercise on microglia, behavioral performance, and neural efficiency. Microglia, the immune cells of the brain, were examined because they help heal the damaged brain; however, their activation is also implicated in the neurotoxic effects of chronic alcohol consumption. Exercise beginning seven days after the binge was found to increase the number of microglia displaying a partially activated morphology in the mPFC, an effect that was not seen in animals waiting 35 days to begin exercise. This suggests binge alcohol was priming microglia to be more responsive to exercise. Due to increased microglial priming and susceptibility to alcohol-induced damage in females, sex differences in response to binge alcohol and exercise were also assessed. Binged females had an increase in microglia and had more microglia with a partially activated morphology compared to binged males. Moreover, females had a higher baseline expression of MHC II+ microglia that significantly increased when females both binged and exercised. This increased reactivity of microglia to alcohol in females may contribute to the increased susceptibility of females to alcohol-induced neural damage. Finally, neural efficiency during a spatial learning task was assessed. Binge alcohol reduced neural efficiency in the mPFC of animals on the last day of water maze testing, without impairing spatial learning. Exercise following binge alcohol resulted in perseverative-like behavior during the probe trial and altered patterns of neural activation in the mPFC and DG. We conclude that exercise has a differential effect on microglia reactivity and neural processing while alcohol is still influencing the brain.