Transgenic mice with increased astrocyte expression of CCL2 show altered behavioral effects of alcohol.
Transgenic mice with increased astrocyte expression of CCL2 show altered behavioral effects of alcohol.
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DOI：
10.1016/j.neuroscience.2017.04.009
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发表时间：
2017-06-23
期刊：
影响因子：
3.3
通讯作者：
Gruol DL
中科院分区：
文献类型：
--
作者：
Bray JG;Roberts AJ;Gruol DL
新兴研究提供了强有力的证据，表明中枢神经系统胶质细胞的激活发生在神经系统疾病和脑损伤中，并导致神经免疫因子的产生升高。这些因素可以促进导致中枢神经系统功能改变的病理生理过程。最近的研究还表明，急性和慢性饮酒均可产生中枢神经系统胶质细胞的激活和神经免疫因子的产生，特别是趋化因子CCL2。酒精诱导CCL2水平在中枢神经系统中升高的后果尚未完全阐明。我们的研究集中在CCL2在中枢神经系统中的水平升高产生神经适应性变化，从而改变酒精对中枢神经系统的作用这一假设上。我们在表达CCL2水平升高的转基因小鼠中使用行为测试来验证这一假设。转基因小鼠中CCL2水平的升高涉及星形胶质细胞表达的增加。转基因小鼠和它们的非转基因同伴对照接受两种酒精暴露模式中的一种，一种是不产生酒精依赖的两瓶选择酒精饮用过程，另一种是产生酒精依赖的慢性间歇性酒精饮用过程。行为测试包括Barnes迷宫、y迷宫、提示和情境条件恐惧测试、明暗转移和强迫游泳测试。酒精naïve、非依赖性、酒精依赖性CCL2转基因小鼠和非tg小鼠之间的比较表明，CCL2水平升高与酒精在饮酒、空间学习和联想学习测试中的相互作用。
Emerging research provides strong evidence that activation of CNS glial cells occurs in neurological diseases and brain injury and results in elevated production of neuroimmune factors. These factors can contribute to pathophysiological processes that lead to altered CNS function. Recently, studies have also shown that both acute and chronic alcohol consumption can produce activation of CNS glial cells and the production of neuroimmune factors, particularly the chemokine CCL2. The consequences of alcohol-induced increases in CCL2 levels in the CNS have yet to be fully elucidated. Our studies focus on the hypothesis that increased levels of CCL2 in the CNS produce neuroadaptive changes that modify the actions of alcohol on the CNS. We utilized behavioral testing in transgenic mice that express elevated levels of CCL2 to test this hypothesis. The increased level of CCL2 in the transgenic mice involves increased astrocyte expression. Transgenic mice and their non-transgenic littermate controls were subjected to one of two alcohol exposure paradigms, a two-bottle choice alcohol drinking procedure that does not produce alcohol dependence or a chronic intermittent alcohol procedure that produces alcohol dependence. Several behavioral tests were carried out including the Barnes Maze, Y-Maze, cued and contextual conditioned fear test, light-dark transfer, and forced swim test. Comparisons between alcohol naïve, non-dependent, and alcohol dependent CCL2 transgenic and non-tg mice show that elevated levels of CCL2 in the CNS interact with alcohol in tests for alcohol drinking, spatial learning and associative learning.
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影响因子：
3.4
作者：
Griffin, William C., III;Lopez, Marcelo F.;Yanke, Amy B.;Middaugh, Lawrence D.;Becker, Howard C.
通讯作者：
Becker, Howard C.
影响因子：
4.1
作者：
Gould, TJ
通讯作者：
Gould, TJ
影响因子：
64.5
作者：
BEACH, ME;HAWKINS, RD;MAYFORD, M
通讯作者：
MAYFORD, M
影响因子：
3.3
作者：
Chang, G. -Q.;Karatayev, O.;Leibowitz, S. F.
通讯作者：
Leibowitz, S. F.
影响因子：
3.7
作者：
Edman, Linda C.;Mira, Helena;Arenas, Ernest
通讯作者：
Arenas, Ernest