Synaptic plasticity in the hippocampus shows resistance to acute ethanol exposure in transgenic mice with astrocyte-targeted enhanced CCL2 expression.
Synaptic plasticity in the hippocampus shows resistance to acute ethanol exposure in transgenic mice with astrocyte-targeted enhanced CCL2 expression.
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DOI：
10.1016/j.neuropharm.2012.11.007
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发表时间：
2013-04
影响因子：
4.7
通讯作者：
Gruol DL
中科院分区：
文献类型：
--
作者：
Bray JG;Reyes KC;Roberts AJ;Ransohoff RM;Gruol DL
已经表明，乙醇暴露可以激活星形胶质细胞和小胶质细胞，导致产生神经免疫因子，包括趋化因子CCL2。这些神经免疫因子在乙醇对中枢神经系统影响中的作用尚未阐明。为了解决这个问题，我们研究了乙醇对海马中突触传递和可塑性的影响，这些海马来自大脑中CCL2表达水平升高的小鼠及其非转基因同窝对照。转基因小鼠的大脑模拟了酒精大脑的一个方面，慢性增加的CCL2水平。我们使用细胞外场电位记录急性分离海马切片，以确定由CCL2水平升高产生的神经适应性变化，以及这些神经适应性变化如何影响急性乙醇的作用。结果表明，在CCL 2转基因和非转基因海马的突触传递和乙醇对突触传递的影响是相似的。然而，长时程增强（LTP），一种被认为是学习和记忆基础的细胞机制，在CCL2转基因海马体中对在非转基因海马体中观察到的乙醇诱导的LTP抑制具有抗性。与这些结果一致，乙醇预处理显着损害线索和上下文的恐惧条件在非转基因小鼠，但没有影响在CCL2转基因小鼠。这些数据表明，慢性升高水平的CCL 2在海马产生神经适应性的变化，阻断了抑郁症的影响，乙醇对海马突触可塑性和支持的假设，CCL 2可能提供了一个神经保护作用，对破坏性的行动，乙醇对海马功能。
It has been shown that ethanol exposure can activate astrocytes and microglia resulting in the production of neuroimmune factors, including the chemokine CCL2. The role of these neuroimmune factors in the effects of ethanol on the central nervous system has yet to be elucidated. To address this question, we investigated the effects of ethanol on synaptic transmission and plasticity in the hippocampus from mice that express elevated levels of CCL2 in the brain and their non-transgenic littermate controls. The brains of the transgenic mice simulate one aspect of the alcoholic brain, chronically increased levels of CCL2. We used extracellular field potential recordings in acutely isolated hippocampal slices to identify neuroadaptive changes produced by elevated levels of CCL2 and how these neuroadaptive changes affect the actions of acute ethanol. Results showed that synaptic transmission and the effects of ethanol on synaptic transmission were similar in the CCL2-transgenic and nontransgenic hippocampus. However, long-term potentiation (LTP), a cellular mechanism thought to underlie learning and memory, in the CCL2-transgenic hippocampus was resistant to the ethanol-induced depression of LTP observed in the non-transgenic hippocampus. Consistent with these results, ethanol pretreatment significantly impaired cued and contextual fear conditioning in non-transgenic mice, but had no effect in CCL2-transgenic mice. These data show that chronically elevated levels of CCL2 in the hippocampus produce neuroadaptive changes that block the depressing effects of ethanol on hippocampal synaptic plasticity and support the hypothesis that CCL2 may provide a neuroprotective effect against the devastating actions of ethanol on hippocampal function.
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影响因子：
4.1
作者：
Gould, TJ
通讯作者：
Gould, TJ
影响因子：
3.2
作者：
Erickson MA;Maramara LA;Lisman J
通讯作者：
Lisman J
影响因子：
4.7
作者：
Bertollini, Cristina;Ragozzino, Davide;Eusebi, Fabrizio
通讯作者：
Eusebi, Fabrizio
DOI：
10.1073/pnas.95.18.10896
发表时间：
1998-09-01
影响因子：
11.1
作者：
Harrison, JK;Jiang, Y;Feng, LL
通讯作者：
Feng, LL
影响因子：
3.7
作者：
Kiyota T;Yamamoto M;Xiong H;Lambert MP;Klein WL;Gendelman HE;Ransohoff RM;Ikezu T
通讯作者：
Ikezu T