Adolescent binge alcohol exposure induces long-lasting partial activation of microglia.
Adolescent binge alcohol exposure induces long-lasting partial activation of microglia.
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DOI：
10.1016/j.bbi.2011.01.006
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发表时间：
2011-06
影响因子：
15.1
通讯作者：
Nixon, Kimberly
中科院分区：
文献类型：
--
作者：
McClain, Justin A.;Morris, Stephanie A.;Deeny, M. Ayumi;Marshall, S. Alex;Hayes, Dayna M.;Kiser, Zachary M.;Nixon, Kimberly
越来越多的证据表明，青少年海马是高度敏感的酒精引起的结构损伤和行为缺陷。小胶质细胞是支持和维持正常神经功能所需的至关重要的大脑成分;然而，酒精对小胶质细胞的影响直到最近才得到关注。在青春期的小胶质细胞对酒精的反应还有待研究，因此，我们研究了海马小胶质细胞激活的青春期酗酒暴露模型。对青春期雄性Sprague-Dawley大鼠给予乙醇，每天3次，持续4天，并在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。使用小胶质细胞标记物Iba-1对小胶质细胞形态进行评分，同时使用艾德-1、主要组织相容性复合物-II（MHC-II）和肿瘤坏死因子（TNF）-α表达检查小胶质细胞活化程度。乙醇诱导海马小胶质细胞发生显著的形态学变化，与激活一致。此外，乙醇增加BrdU+细胞的数量在所有区域的海马后2天的最后一次剂量。共聚焦显微镜观察显示，各区域增殖的BrdU+细胞均为Iba-1+小胶质细胞。重要的是，新出生的小胶质细胞存活，并保留其形态特征后30天乙醇暴露。乙醇并没有改变海马艾德-1、MHC-II或TNF-α的表达，这表明单次酒精过量暴露不会诱导完全的小胶质细胞驱动的神经炎症反应。这些结果表明，乙醇触发了青少年海马体中持续到成年早期的部分小胶质细胞激活，这表明在这个独特的发育时期暴露于酒精具有长期的后果。
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 histocompatability 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.
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影响因子：
3.5
作者：
Morris, Stephanie A.;Eaves, David W.;Smith, Aleksander R.;Nixon, Kimberly
通讯作者：
Nixon, Kimberly
影响因子：
15.9
作者：
Kreutzberg, GW
通讯作者：
Kreutzberg, GW
影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
影响因子：
5.3
作者：
Alfonso-Loeches, Silvia;Pascual-Lucas, Maya;Guerri, Consuelo
通讯作者：
Guerri, Consuelo
DOI：
10.1016/s0169-328x(98)00040-0
发表时间：
1998-06-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Ito, D;Imai, Y;Kohsaka, S
通讯作者：
Kohsaka, S