Department of Pharmaceutical Sciences, The University of Kentucky, Lexington, KY 40536, USA.
Brain Behav Immun. 2011 Jun;25 Suppl 1(Suppl 1):S120-8. doi: 10.1016/j.bbi.2011.01.006. Epub 2011 Jan 22.
Accumulating evidence indicates that the adolescent hippocampus is highly susceptible to alcohol-induced structural damage and behavioral deficits. Microglia are vitally important brain constituents needed to support and maintain proper neural function; however, alcohol's effects on microglia have only recently gained attention. The microglial response to alcohol during adolescence has yet to be studied; therefore, we examined hippocampal microglial activation in an adolescence binge alcohol exposure model. Adolescent male Sprague-Dawley rats were administered ethanol 3 times/day for 4 days and were sacrificed 2, 7, and 30 days later. Bromo-deoxy-Uridine was injected 2 days after ethanol exposure to label dividing cells. Microglia morphology was scored using the microglia marker Iba-1, while the extent of microglial activation was examined with ED-1, major histocompatibility complex-II (MHC-II), and tumor necrosis factor (TNF)-α expression. Ethanol induced significant morphological change in hippocampal microglia, consistent with activation. In addition, ethanol increased the number of BrdU+ cells throughout all regions of the hippocampus 2 days after the last dose. Confocal microscopy showed that the proliferating BrdU+ cells in each region were Iba-1+ microglia. Importantly, newly born microglia survived and retained their morphological characteristics 30 days after ethanol exposure. Ethanol did not alter hippocampal ED-1, MHC-II, or TNF-α expression, suggesting that a single period of binge ethanol exposure does not induce a full microglial-driven neuroinflammatory response. These results establish that ethanol triggers partial microglial activation in the adolescent hippocampus that persists through early adulthood, suggesting that alcohol exposure during this unique developmental time period has long-lasting consequences.
越来越多的证据表明，青少年时期的海马体极易受到酒精引起的结构损伤和行为缺陷的影响。小胶质细胞是维持正常神经功能所必需的重要脑成分，但酒精对小胶质细胞的影响直到最近才引起关注。酒精对青春期小胶质细胞的影响尚未得到研究；因此，我们在青春期 binge 酒精暴露模型中研究了海马体小胶质细胞的激活。青春期雄性 Sprague-Dawley 大鼠每天接受 3 次乙醇治疗，共 4 天，然后在 2、7 和 30 天后处死。在乙醇暴露后 2 天注射溴脱氧尿苷以标记分裂细胞。使用小胶质细胞标志物 Iba-1 对小胶质细胞形态进行评分，同时用 ED-1、主要组织相容性复合体-II（MHC-II）和肿瘤坏死因子（TNF）-α表达检查小胶质细胞的激活程度。乙醇诱导海马体小胶质细胞发生显著的形态变化，与激活一致。此外，乙醇在最后一次给药后 2 天增加了海马体所有区域的 BrdU+细胞数量。共聚焦显微镜显示，每个区域中的增殖 BrdU+细胞都是 Iba-1+小胶质细胞。重要的是，新生的小胶质细胞在乙醇暴露 30 天后存活并保持其形态特征。乙醇未改变海马体 ED-1、MHC-II 或 TNF-α的表达，这表明单次 binge 乙醇暴露不会引起完整的小胶质细胞驱动的神经炎症反应。这些结果表明，乙醇在青春期海马体中引发部分小胶质细胞激活，这种激活持续到成年早期，表明在这一独特的发育时期暴露于酒精会产生持久的后果。
