Astrocytic responses to binge ethanol in male and female mice: An examination of astrocytic glutamate transporters and density changes in the dorsal hippocampus.

BACKGROUND: Excessive alcohol consumption has been associated with a proinflammatory neuroimmune response and deficits in glutamate transporters. While astrocytes regulate the neuroimmune response and glutamatergic tone, estrogen can promote neuroprotective and neurotrophic effects on astrocytes. However, studies in alcohol use disorders (AUDs) have primarily focused on males, and given the more escalated rate at which females display signs of AUDs compared with males, this study examines sex-based differences in astrocytic responses to ethanol following a nondependent binge drinking paradigm. METHODS: Male and female mice consumed either 20% ethanol (v/v) or 3% sucrose (w/v) for three cycles in the Drinking in the Dark paradigm. The brains of these mice were collected for immunohistochemistry and qRT-PCR for markers of astrocyte activity, cytokines, and astrocytic glutamate transporters. ELISAs were performed on hippocampal tissue to measure cytokines and glutamate transporters. RESULTS: Ethanol exposure caused an increase in glial fibrillary acidic protein (GFAP) immunoreactivity and GFAP+ cell counts in the hippocampus that were more robust in females. Ethanol's influence on S100B+ cell counts was subregional and sex-specific. Changes in astrocytes were accompanied by a decrease in glutamate transporter 1 (GLT-1) mRNA but not protein with no changes in glutamate aspartate transporter (GLAST). However, cystine/glutamate antiporter (xCT) expression increased specifically in female mice days following ethanol exposure. CONCLUSIONS: These data suggest that nondependent binge drinking alters astrocytes in the hippocampus that can lead to dysregulation of glutamate transporters and cytokine synthesis. Moreover, there were sex-specific effects shown in binge-like exposure's effects, highlighting the need to consider sex as a biological variable in the neuroimmune response in AUDs.