Prior Binge Ethanol Exposure Potentiates the Microglial Response in a Model of Alcohol-Induced Neurodegeneration.
Prior Binge Ethanol Exposure Potentiates the Microglial Response in a Model of Alcohol-Induced Neurodegeneration.
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DOI：
10.3390/brainsci6020016
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发表时间：
2016-05-26
期刊：
影响因子：
3.3
通讯作者：
Nixon K
中科院分区：
文献类型：
--
作者：
Marshall SA;Geil CR;Nixon K
过量饮酒会导致神经变性，有些人认为这是由神经炎症引起的。神经炎症的一个特征是小胶质细胞的激活，但现在人们普遍认为小胶质细胞的激活可能是促炎或抗炎的。最近的工作表明，Majchrowicz酒精诱导的神经变性模型会导致抗炎小胶质细胞，而间歇性接触较低剂量和血液酒精水平的模型会产生具有促炎表型的小胶质细胞。为了确定反复酗酒的影响，大鼠接受了为期四天的Majchrowicz模型的两个周期。然后，一个大脑半球用于通过免疫组织化学方法评估小胶质细胞，另一个大脑半球用于细胞因子和生长因子的ELISA。一次过量的酒精暴露导致低水平的小胶质细胞激活；然而，第二次暴饮暴食增强了小胶质细胞的反应。与单次酗酒组相比，双饮组大鼠OX-42免疫反应增强，离子钙结合适配器分子1(IBA-1+)细胞增多，肿瘤坏死因子-α(TNF-α)表达上调。这些数据表明，先前的酒精暴露增强了随后的小胶质细胞反应，这表明最初的酒精暴露启动了小胶质细胞。总而言之，与其他免疫调节事件无关的反复酒精暴露会增强小胶质细胞的活性。
Excessive alcohol consumption results in neurodegeneration which some hypothesize is caused by neuroinflammation. One characteristic of neuroinflammation is microglial activation, but it is now well accepted that microglial activation may be pro- or anti-inflammatory. Recent work indicates that the Majchrowicz model of alcohol-induced neurodegeneration results in anti-inflammatory microglia, while intermittent exposure models with lower doses and blood alcohol levels produce microglia with a pro-inflammatory phenotype. To determine the effect of a repeated binge alcohol exposure, rats received two cycles of the four-day Majchrowicz model. One hemisphere was then used to assess microglia via immunohistochemistry and while the other was used for ELISAs of cytokines and growth factors. A single binge ethanol exposure resulted in low-level of microglial activation; however, a second binge potentiated the microglial response. Specifically, double binge rats had greater OX-42 immunoreactivity, increased ionized calcium-binding adapter molecule 1 (Iba-1+) cells, and upregulated tumor necrosis factor-α (TNF-α) compared with the single binge ethanol group. These data indicate that prior ethanol exposure potentiates a subsequent microglia response, which suggests that the initial exposure to alcohol primes microglia. In summary, repeated ethanol exposure, independent of other immune modulatory events, potentiates microglial activity.