Microglial activation in the dorsal striatum participates in anxiety-like behavior in Cyld knockout mice
Microglial activation in the dorsal striatum participates in anxiety-like behavior in Cyld knockout mice
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背侧纹状体中的小胶质细胞激活参与 Cyld 敲除小鼠的焦虑样行为
DOI：
10.1016/j.bbi.2020.07.011
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发表时间：
2020-10-01
影响因子：
15.1
通讯作者：
Long, Cheng
中科院分区：
文献类型：
--
作者：
Han, Yuan-Yuan;Jin, Kai;Long, Cheng
CyLD赖氨酸63脱泛素酶(CyLD)主要参与免疫反应和炎症反应，在脑内特别是背侧纹状体高水平表达，但其在脑内的生理功能尚不清楚。本研究探讨了CyLD基因敲除对与背侧纹状体相关的行为的影响，如运动活动、类抑郁和类焦虑行为。对小胶质细胞和促炎细胞因子包括白介素1β和肿瘤坏死因子α在背侧纹状体内进行检测，以阐明其可能的机制。CyLD基因敲除(CyLD(-/-))小鼠表现出焦虑样行为，但没有运动缺陷或抑郁样行为。与CyLD(+/+)小鼠相比，CyLD(-/-)小鼠背侧纹状体小胶质细胞被激活，IL-1β和TNF-α的mRNA水平升高。小胶质细胞调节剂米诺环素部分逆转了CyLD(-/-)小鼠的焦虑样行为、小胶质细胞的激活以及IL-1β和TNF-αmRNA和蛋白水平的升高。综上所述，这些结果表明，导致小胶质细胞激活的CyLD基因敲除促进了IL-1β和TNF-α的表达，并在焦虑的病理生理学中发挥了关键作用。
CYLD lysine 63 deubiquitinase (CYLD), that is mainly involved in immune responses and inflammation, is expressed at high levels in the brain, especially in the dorsal striatum, but its physiological function of CYLD in the brain remains unexplored. The present study investigated the effect of Cyld gene knockout on behavior relevant to the dorsal striatum, such as motor activity and depression-like and anxiety-like behavior. Microglia and the pro-inflammatory cytokines including interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha were evaluated in the dorsal striatum to elucidate the underlying mechanism. Cyld knockout (Cyld(-/-)) mice exhibited anxiety-like behavior, but not motor deficits or depression-like behavior. Microglia were activated and the mRNA levels of IL1 beta and TNF-alpha were increased in the dorsal striatum of Cyld(-/-) mice compared to Cyld(+/+) mice. The microglial modulator minocycline partially reversed the anxiety-like behavior, microglial activation and increase in IL-1 beta and TNF-alpha mRNA and protein levels in the dorsal striatum of Cyld(-/-) mice. Collectively, these results suggest that Cyld knockout leading to microglial activation promotes IL-1 beta and TNF-alpha expression and acts as a critical pathway in the pathophysiology of anxiety.