OBJECTIVES Alcohol dependence leads to dysregulation of the neuroimmune system, but the effects of excessive alcohol consumption on key players of the neuroimmune response after episodic binge drinking in nondependence has not been readily assessed. These studies seek to determine how the neuroimmune system within the hippocampus responds to binge-like consumption prior to dependence or evidence of brain damage. METHODS C57BL/6J mice underwent the drinking in the dark (DID) paradigm to recapitulate binge consumption. Immunohistochemical techniques were employed to determine the effects of ethanol on cytokine and astrocyte responses within the hippocampus. Astrocyte activation was also assessed using qRT-PCR. RESULTS Our results indicated that binge-like ethanol consumption resulted in a 3.6-fold increase in the proinflammatory cytokine interleukin (IL)-1β immunoreactivity in various regions of the hippocampus. The opposite effect was seen in the anti-inflammatory cytokine IL-10. Binge-like consumption resulted in a 67% decrease in IL-10 immunoreactivity but had no effect on IL-4 or IL-6 compared with the water-drinking control group. Moreover, astrocyte activation occurred following ethanol exposure as GFAP immunoreactivity was increased over 120% in mice that experienced 3 cycles of ethanol binges. PCR analyses indicated that the mRNA increased by almost 4-fold after one cycle of DID, but this effect did not persist in abstinence. CONCLUSIONS Altogether, these findings suggest that binge-like ethanol drinking prior to dependence causes dysregulation to the neuroimmune system. This altered neuroimmune state may have an impact on behavior but could also result in a heightened neuroimmune response that is exacerbated from further ethanol exposure or other immune-modulating events.

中文翻译：

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在黑暗模型中饮酒对海马样乙醇消费的海马神经免疫反应的表征。

目的酒精依赖会导致神经免疫系统失调，但尚不容易评估过度饮酒对非依赖性发作性暴饮后神经免疫反应关键参与者的影响。这些研究试图确定在依赖或脑损伤之前，海马内的神经免疫系统如何应对暴饮暴食。方法C57BL / 6J小鼠在黑暗（DID）模式下饮酒以概括暴饮暴食。免疫组织化学技术被用来确定乙醇对海马细胞因子和星形胶质细胞反应的影响。还使用qRT-PCR评估星形胶质细胞的活化。结果我们的结果表明，暴饮般的乙醇消耗导致3。海马不同区域的促炎细胞因子白介素（IL）-1β免疫反应性增加了6倍。在抗炎细胞因子IL-10中观察到相反的作用。与饮水对照组相比，暴饮暴食导致IL-10免疫反应性降低67％，但对IL-4或IL-6没有影响。此外，星形胶质细胞活化发生在乙醇暴露后，因为经历了3次乙醇暴饮的小鼠中GFAP免疫反应性增加了120％以上。PCR分析表明，DID的一个周期后，mRNA增加了几乎4倍，但这种作用并未持续。结论总而言之，这些发现表明在依赖之前喝暴饮般的乙醇会导致神经免疫系统失调。