Estrogen protects against ethanol-induced astrocytic response in dorsal hippocampus but not ethanol-induced liver inflammation in ovariectomized mice.

Sex has been shown to play a dynamic role in the responses to alcohol, with women often being cited as having more detrimental consequences from alcohol use. The current increasing rates of alcohol drinking by women, including women over 50, highlights the importance of studying the participation of sex hormones in the effects of alcohol misuse. Alcohol is known to produce both central and peripheric inflammation, but the interaction between alcohol and estradiol is poorly understood. To test the interaction between estradiol and ethanol, ovariectomized mice received ethanol (1.5 g/kg) or sucrose by oral gavage with concomitant subcutaneous estradiol benzoate (10 µg/kg) or vehicle, during the whole ethanol treatment period. To assess the neuroimmune response, glial fibrillary acidic protein (GFAP) was used as a marker of reactive astrocytes in the dorsal hippocampus. For peripheric inflammation, the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) was quantified in the liver. Estradiol prevented the increase in number but not immunoreactivity of GFAP positive astrocytes, suggesting that estrogen may partially protect from ethanol-induced neuroinflammation. On the other hand, estradiol had no effect on MCP-1 levels suggesting estradiol's protective effects do not extend to ethanol-induced liver inflammation. These results show that estrogen can have different effects on alcohol-induced inflammatory responses. Further studies are necessary to elucidate the interaction between alcohol and sex hormones on inflammatory signaling.