Astrocyte modulation of extinction impairments in ethanol-dependent female mice.

Astrocyte modulation of extinction impairments in ethanol-dependent female mice.
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酒精依赖雌性小鼠中星形胶质细胞对消退障碍的调节。

DOI:
10.1016/j.neuropharm.2020.108272
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发表时间:
2020-11-15
期刊:
影响因子:
4.7
通讯作者:
Barker JM
Barker JM
中科院分区:
医学2区
文献类型:
--
作者:
Giacometti LL;Chandran K;Figueroa LA;Barker JM

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妇女中酒精使用障碍的比率正在增加,越来越多的证据表明,与男子相比,妇女对酒精依赖的认知和生理后果都是不同的。尽管如此,在女性和雌性动物中,慢性酒精暴露的神经行为结果却没有得到很好的表征。在这项研究中,我们发现乙醇依赖损害了雌性小鼠在食物条件下的位置偏好任务中寻求奖励的消退。在同一时间点,乙醇依赖的女性表现出星形胶质细胞失调,这是脑区域特异性胶质纤维酸性蛋白(GFAP)表达减少所表明的。利用化学发生策略,我们证明了通过化学发生激活伏隔核星形胶质细胞的gq信号来调节星形胶质细胞的功能,在不影响基础奖励寻求的情况下,短暂地拯救了乙醇依赖的雌性星形胶质细胞的灭绝。这些发现确定星形胶质细胞功能是女性慢性酒精暴露后行为灵活性恢复的潜在目标。
Rates of alcohol use disorders are increasing in women, and there is growing evidence that both the cognitive and biological consequences of alcohol dependence are distinct in women as compared to men. Despite this, the neurobehavioral outcomes of chronic alcohol exposure are poorly characterized in women and female animals. In this study, we find that ethanol dependence impaired extinction of reward seeking in a food conditioned place preference task in female mice. At the same time point, ethanol-dependent females exhibited astrocytic dysregulation as indicated by a brain region-specific reduction in glial fibrillary acidic protein (GFAP) expression. Using a chemogenetic strategy, we demonstrate that modulating astrocyte function via chemogenetic activation of Gq-signaling in nucleus accumbens astrocytes transiently rescued extinction in ethanol-dependent females without impacting basal reward seeking. These findings identify astrocyte function as a potential target for the restoration of behavioral flexibility following chronic alcohol exposure in females.
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