Department of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA.
Department of Basic Pharmaceutical Sciences, Fred P. Wilson School of Pharmacy, High Point University, High Point, NC 27268, USA.
J Integr Neurosci. 2021 Dec 30;20(4):933-943. doi: 10.31083/j.jin2004094.
Alcoholism causes various maladaptations in the central nervous system, including the neuroimmune system. Studies of alcohol-induced dysregulation of the neuroimmune system generally focus on alcohol dependence and brain damage, but our previous research indicates that repetitive binge-like consumption perturbs cytokines independent of cell death. This paper extends that research by examining the impact of binge-like consumption on microglia in the hippocampus and the amygdala. Microglia were assessed using immunohistochemistry following binge-like ethanol consumption based on Drinking-in-the-Dark model. Immunohistochemistry results showed that binge-like ethanol consumption caused an increase in Iba-1 immunoreactivity and the number of Iba-1+ cells after one Drinking-in-the-Dark cycle. However, after three Drinking-in-the-Dark cycles, the number of microglia decreased in the hippocampus. We showed that in the dentate gyrus, the average immunoreactivity/cell was increased following ethanol exposure despite the decrease in number after three cycles. Likewise, Ox-42, an indicator of microglia activation, was upregulated after ethanol consumption. No significant effects on microglia number or immunoreactivity (Iba-1 nor Ox-42) were observed in the amygdala. Finally, ethanol caused an increase in the expression of the microglial gene Aif-1 during intoxication and ten days into abstinence, suggesting persistence of ethanol-induced upregulation of microglial genes. Altogether, these findings indicate that repetitive binge-like ethanol is sufficient to elicit changes in microglial reactivity. This altered neuroimmune state may contribute to the development of alcohol use disorders.
酒精中毒会导致中枢神经系统的各种适应不良，包括神经免疫系统。研究酒精引起的神经免疫失调通常集中在酒精依赖和大脑损伤上，但我们之前的研究表明，重复性 binge-like 消费会扰乱细胞死亡以外的细胞因子。本文通过研究 binge-like 消费对海马体和杏仁核中小胶质细胞的影响，扩展了这一研究。根据暗饮模型，在 binge-like 乙醇消费后，使用免疫组织化学评估小胶质细胞。免疫组织化学结果表明， binge-like 乙醇消费导致一次暗饮周期后 Iba-1 免疫反应性和 Iba-1+细胞数量增加。然而，在三个暗饮周期后，海马体中小胶质细胞数量减少。我们表明，在齿状回中，尽管在三个周期后数量减少，但乙醇暴露后平均免疫反应性/细胞增加。同样，Ox-42（小胶质细胞活化的指标）在乙醇消耗后上调。在杏仁核中，小胶质细胞数量或免疫反应性（Iba-1 或 Ox-42）没有观察到显著影响。最后，乙醇在中毒期间和戒断十天后导致小胶质细胞基因 Aif-1 的表达增加，表明小胶质细胞基因的乙醇诱导上调持续存在。总之，这些发现表明，重复性 binge-like 乙醇足以引起小胶质细胞反应性的变化。这种改变的神经免疫状态可能有助于酒精使用障碍的发展。
