Sex differences in the neuroimmune response following heavy, binge-like alcohol exposure in adolescent rats

Adolescents who consume alcohol show a high prevalence of binge drinking, which has been linked to brain damage and neuroimmune reactions that increase risk for developing an alcohol use disorder (AUD). Adolescent female drinking patterns have surpassed males, yet little is known about damaging effects of alcohol in females. Known sex differences in neuroimmune reactivity, specifically microglial reactivity, suggest that the female brain will differ from males. Therefore, we examined indicators of neuroimmune activation and neurodegeneration following 2 days of heavy, bingelike exposure in adolescent male and female rats. Translocator protein 18kD (TSPO) expression assessed by [³H]PK-11195 autoradiography revealed that adolescent female rats showed a brief and immediate response in the thalamus, while male rats showed a delayed and sustained increase in the thalamus and hippocampus versus same-sex controls. Neurodegeneration assessed by Fluoro-Jade-B (FJB) dye showed that alcohol-induced cell death was modest for both sexes. Males showed cell death in the entorhinal cortex while females showed greater cell death in the perirhinal and piriform cortices. Additional neuroimmune measures of pro-inflammatory cytokine, IL-6, was decreased in the hippocampus and entorhinal cortex a week after alcohol exposure in females only. No changes in brain-derived neurotrophic factor (BDNF) were found in either sex or region. Overall, these experiments show adolescent females and males display unique neuroimmune responses and neurodegeneration profiles following heavy binge-like exposure. These data imply that females show a impaired neuroimmune response to alcohol that could contribute to sex differences in damage and deficits caused by alcohol.