Alterations in circulating extracellular vesicles underlie social stress-induced behaviors in mice.
Alterations in circulating extracellular vesicles underlie social stress-induced behaviors in mice.
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DOI：
10.1002/2211-5463.13204
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发表时间：
2021-10
期刊：
影响因子：
2.6
通讯作者：
Kano SI
中科院分区：
文献类型：
--
作者：
Sakamoto S;Mallah D;Medeiros DJ;Dohi E;Imai T;Rose IVL;Matoba K;Zhu X;Kamiya A;Kano SI
慢性应激诱导外周和脑内免疫改变和炎症，导致与抑郁症等精神疾病相关的神经病理和行为异常。尽管许多外周因子（如促炎细胞因子、激素和巨噬细胞）的病理意义已被证实，但循环细胞外囊泡（EVs）在慢性应激机制中的作用仍未得到充分研究。在这里，我们报告了慢性社会失败压力（CSDS）诱导的社会回避表型，通过以前未测试的三室社会方法测试来评估，可以通过血液中的多种促炎细胞因子和EV相关的分子特征来区分。我们发现mirna的表达模式区分了CSDS易感小鼠和CSDS恢复小鼠。通过多个EV相关mirna的表达模式，也可以很准确地估计社交回避行为得分。我们还证明，在LPS刺激的小胶质样细胞系中，从CSDS易感小鼠血清中富集的ev上调了促炎性细胞因子的产生。我们的研究结果表明，循环ev和相关mirna在CSDS易感性中的作用，这可能与应激诱导的神经行为结果的促炎机制有关。慢性社会失败应激后的社会回避行为伴随着血液中细胞外囊泡（EVs）的改变，以及促炎细胞因子水平的升高。EV相关的miRNA表达模式与社会行为得分相关。此外，研究显示ev可促进培养的小胶质样细胞中促炎细胞因子的产生。因此，ev可能有助于社交应激小鼠的促炎症反应。
Chronic stress induces peripheral and intracerebral immune changes and inflammation, contributing to neuropathology and behavioral abnormalities relevant to psychiatric disorders such as depression. Although the pathological implication of many peripheral factors such as pro‐inflammatory cytokines, hormones, and macrophages has been demonstrated, the roles of circulating extracellular vesicles (EVs) for chronic stress mechanisms remain poorly investigated. Here, we report that chronic social defeat stress (CSDS)‐induced social avoidance phenotype, assessed by a previously untested three‐chamber social approach test, can be distinguished by multiple pro‐inflammatory cytokines and EV‐associated molecular signatures in the blood. We found that the expression patterns of miRNAs distinguished the CSDS‐susceptible mice from the CSDS‐resilient mice. Social avoidance behavior scores were also estimated with good accuracy by the expression patterns of multiple EV‐associated miRNAs. We also demonstrated that EVs enriched from the CSDS‐susceptible mouse sera upregulated the production of pro‐inflammatory cytokines in the LPS‐stimulated microglia‐like cell lines. Our results indicate the role of circulating EVs and associated miRNAs in CSDS susceptibility, which may be related to pro‐inflammatory mechanisms underlying stress‐induced neurobehavioral outcomes. Social avoidance behaviors after chronic social defeat stress are accompanied by altered extracellular vesicles (EVs) in the blood, together with increased levels of pro‐inflammatory cytokines. EV‐associated miRNA expression patterns are correlated with social behavioral scores. In addition, EVs are shown to enhance the production of pro‐inflammatory cytokines in cultured microglia‐like cells. Thus, EVs may contribute to pro‐inflammatory responses in socially stressed mice.
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影响因子：
16
作者：
Imai T;Takahashi Y;Nishikawa M;Kato K;Morishita M;Yamashita T;Matsumoto A;Charoenviriyakul C;Takakura Y
通讯作者：
Takakura Y
星形胶质细胞衍生的 ATP 调节抑郁样行为
影响因子：
82.9
作者：
Cao, Xiong;Li, Liang-Ping;Gao, Tian-Ming
通讯作者：
Gao, Tian-Ming
DOI：
10.1073/pnas.1209414109
发表时间：
2012-07-31
影响因子：
11.1
作者：
Fabbri, Muller;Paone, Alessio;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
影响因子：
3.7
作者：
He, Zhonghua;Wang, Haixia;Yue, Lingju
通讯作者：
Yue, Lingju
影响因子：
5.3
作者：
Brites D;Fernandes A
通讯作者：
Fernandes A