Sex Differences in Binge Alcohol-Induced Brain Damage and Recovery of Function

Evidence suggests that women are more sensitive to the neurotoxic effects of alcohol and more vulnerable to the adverse medical consequences of heavy alcohol consumption than men. Despite this few studies have directly compared the consequences of binge alcohol between the male and female brain, and the mechanisms that underlie increased female vulnerability remain poorly understood. The present studies investigated sex differences in alcohol-induced neurodegeneration, and associated cognitive deficits and disruption of trophic support, using a rodent model of an alcohol use disorder (AUD). Binge exposure resulted in a significant loss of granule neurons and significantly more degenerating and dead cells in the hippocampal dentate gyrus of females compared to males. This was associated with a binge-induced spatial reference memory deficits in the Morris water maze for females but not males. Binge-induced neurodegeneration in the female hippocampus was associated with a decrease of BDNF, TrkB, CREB, and pCREB protein expression; however only BDNF was disrupted in the hippocampus of males. Further, we investigated if exercise-driven recovery from binge-induced neurodegeneration was associated with increased trophic support. One to two weeks of voluntary exercise reversed the binge-induced reduction of dentate gyrus granule neurons in females, likely via an increase in BDNF, pCREB, and Iba1 (microglia). We conclude that the female hippocampus is more sensitive to binge-induced neurodegeneration and associated cognitive consequences than males, like due to the disruption of protective tropic support. Voluntary exercise however, can enhance endogenous recovery processes by increasing trophic support that aids in recovery.