Microglial activation mediates chronic mild stress-induced depressive- and anxiety-like behavior in adult rats.
Microglial activation mediates chronic mild stress-induced depressive- and anxiety-like behavior in adult rats.
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小胶质细胞激活介导成年大鼠慢性轻度应激诱导的抑郁和焦虑样行为
DOI：
10.1186/s12974-018-1054-3
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发表时间：
2018-01-17
影响因子：
9.3
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Wang YL;Han QQ;Gong WQ;Pan DH;Wang LZ;Hu W;Yang M;Li B;Yu J;Liu Q
抑郁症是一种异质性疾病，导致该疾病的确切神经机制尚未被发现。最近的研究表明，它伴随着神经炎症，其特征尤其是小胶质细胞激活。然而，小胶质细胞的激活及其在神经炎症和压力相关抑郁症中的作用尚不清楚。我们采用多种检测方法来检测慢性轻度应激（CMS）后大鼠海马的神经炎症。雄性 Sprague Dawley (SD) 大鼠接受慢性轻度应激源 12 周。通过使用体内 [18F] DPA-714 正电子发射计算机断层扫描 (PET) 成像、离子钙结合接头分子 1 和易位蛋白 (TSPO) 免疫组织化学以及 NOD 样受体蛋白 3 (NLRP3) 炎症小体和 一些炎症介质。然后，在最后 4 周内对大鼠进行米诺环素治疗，观察其对慢性轻度应激诱发的海马神经炎症和抑郁样行为的影响。结果表明，12 周的慢性轻度应激会诱发显着的抑郁和焦虑样行为，同时引起 PET、免疫荧光染色和蛋白质印迹检测到的海马小胶质细胞激活。同样，在暴露于慢性应激后，海马中也观察到 NLRP3 炎症小体的激活和炎症介质的上调，例如白细胞介素 1β (IL-1β)、IL-6 和 IL-18。有趣的是，慢性轻度应激后海马中的抗炎介质（例如 IL-4 和 IL-10）也有所增加，这可能暗示慢性应激会激活不同类型的小胶质细胞，从而产生促炎细胞因子或抗炎细胞因子。此外，长期米诺环素治疗减轻了慢性应激引起的抑郁样行为，并显着抑制小胶质细胞活化。类似地，在米诺环素治疗组中，NLRP3炎症小体的激活和炎症介质的增加没有表现出或明显不明显。这些结果共同表明，小胶质细胞激活介导慢性轻度应激诱发的抑郁和焦虑样行为以及海马神经炎症。
Depression is a heterogeneous disorder, with the exact neuronal mechanisms causing the disease yet to be discovered. Recent work suggests it is accompanied by neuro-inflammation, characterized, in particular, by microglial activation. However, microglial activation and its involvement in neuro-inflammation and stress-related depressive disorders are far from understood. We utilized multiple detection methods to detect the neuro-inflammation in the hippocampus of rats after exposure to chronic mild stress (CMS). Male Sprague Dawley (SD) rats were subjected to chronic mild stressors for 12 weeks. Microglial activation and hippocampal neuro-inflammation were detected by using a combinatory approach of in vivo [18F] DPA-714 positron emission computed tomography (PET) imaging, ionized calcium-binding adapter molecule 1 and translocator protein (TSPO) immunohistochemistry, and detection of NOD-like receptor protein 3 (NLRP3) inflammasome and some inflammatory mediators. Then, the rats were treated with minocycline during the last 4 weeks to observe its effect on hippocampal neuro-inflammation and depressive-like behavior induced by chronic mild stress. The results show that 12 weeks of chronic mild stress induced remarkable depressive- and anxiety-like behavior, simultaneously causing hippocampal microglial activation detected by PET, immunofluorescence staining, and western blotting. Likewise, activation of NLRP3 inflammasome and upregulation of inflammatory mediators, such as interleukin-1β (IL-1β), IL-6, and IL-18, were also observed in the hippocampus after exposure to chronic stress. Interestingly, the anti-inflammatory mediators, such as IL-4 and IL-10, were also increased in the hippocampus following chronic mild stress, which may hint that chronic stress activates different types of microglia, which produce pro-inflammatory cytokines or anti-inflammatory cytokines. Furthermore, chronic minocycline treatment alleviated the depressive-like behavior induced by chronic stress and significantly inhibited microglial activation. Similarly, the activation of NLRP3 inflammasome and the increase of inflammatory mediators were not exhibited or significantly less marked in the minocycline treatment group. These results together indicate that microglial activation mediates the chronic mild stress-induced depressive- and anxiety-like behavior and hippocampal neuro-inflammation.
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影响因子：
4.1
作者：
Batarseh, Amani;Papadopoulos, Vassilios
通讯作者：
Papadopoulos, Vassilios
DOI：
10.1016/j.bbi.2016.01.017
发表时间：
2016-11
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Chesnokova V;Pechnick RN;Wawrowsky K
通讯作者：
Wawrowsky K
影响因子：
4.7
作者：
Jacobson, Orit;Kiesewetter, Dale O.;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
影响因子：
10.6
作者：
Dowlati, Yekta;Herrmann, Nathan;Lanctot, Krista L.
通讯作者：
Lanctot, Krista L.
影响因子：
7.6
作者：
Hannestad, Jonas;DellaGioia, Nicole;Bloch, Michael
通讯作者：
Bloch, Michael