Binge alcohol alters exercise-driven neuroplasticity.

Exercise is increasingly being used as a treatment for alcohol use disorders (AUD), but the interactive effects of alcohol and exercise on the brain remain largely unexplored. Alcohol damages the brain, in part by altering glial functioning. In contrast, exercise promotes glial health and plasticity. In the present study, we investigated whether binge alcohol would attenuate the effects of subsequent exercise on glia. We focused on the medial prefrontal cortex (mPFC), an alcohol-vulnerable region that also undergoes neuroplastic changes in response to exercise. Adult female Long-Evans rats were gavaged with ethanol (25% w/v) every 8h for 4days. Control animals received an isocaloric, non-alcohol diet. After 7days of abstinence, rats remained sedentary or exercised for 4weeks. Immunofluorescence was then used to label microglia, astrocytes, and neurons in serial tissue sections through the mPFC. Confocal microscope images were processed using FARSIGHT, a computational image analysis toolkit capable of automated analysis of cell number and morphology. We found that exercise increased the number of microglia in the mPFC in control animals. Binged animals that exercised, however, had significantly fewer microglia. Furthermore, computational arbor analytics revealed that the binged animals (regardless of exercise) had microglia with thicker, shorter arbors and significantly less branching, suggestive of partial activation. We found no changes in the number or morphology of mPFC astrocytes. We conclude that binge alcohol exerts a prolonged effect on morphology of mPFC microglia and limits the capacity of exercise to increase their numbers.