Recurrent binge ethanol is associated with significant loss of dentate gyrus granule neurons in female rats despite concomitant increase in neurogenesis

Abstract

Binge drinking is becoming increasingly common among American women and girls. We have previously shown significant cell loss, downregulation of neurotrophins and microgliosis in female rats after a single 4-day ethanol exposure. To determine whether recurrent binge exposure would produce similar effects, we administered ethanol (5 g/kg) or iso-caloric control diet once-weekly for 11 weeks to adult female rats. As we have previously shown exercise neuroprotection against binge-induced damage, half the rats were given access to exercise wheels. Blood ethanol concentration (BEC) did not differ between sedentary and exercised groups, nor did it change across time. Using stereology, we quantified the number and/or size of neurons in the medial prefrontal cortex (mPFC) and hippocampal dentate gyrus (DG), as well as the number and activation state of microglia. Binged sedentary rats had significant cell loss in the dentate gyrus, but exercise eliminated this effect. Compared to sedentary controls, sedentary binged rats and all exercised rats showed increased neurogenesis in the DG. Number and nuclear volume of neurons in the mPFC were not changed. In the hippocampus and mPFC, the number of microglia with morphology indicative of partial activation was increased by recurrent binge ethanol and decreased by exercise. In summary, we show significant binge-induced loss of DG granule neurons despite increased neurogenesis, suggesting an unsuccessful compensatory response. Although exercise eliminated cell loss, our results indicate that infrequent, but recurrent exposure to clinically relevant BEC is neurotoxic.

Keywords: Alcohol; Exercise; Hippocampus; Medial prefrontal cortex; Microglia; Rotarod; Spatial navigation.