Alterations in circulating extracellular vesicles underlie social stress-induced behaviors in mice

被引:20
作者
Sakamoto, Shinji [1 ]
Mallah, Dania [2 ]
Medeiros, Destynie J. [2 ]
Dohi, Eisuke [1 ,2 ]
Imai, Takashi [1 ]
Rose, Indigo V. L. [1 ]
Matoba, Ken [2 ]
Zhu, Xiaolei [1 ]
Kamiya, Atsushi [1 ]
Kano, Shin-ichi [1 ,2 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St, Baltimore, MD 21287 USA
[2] Univ Alabama Birmingham, Birmingham Sch Med, Dept Psychiat & Behav Neurobiol, 1720 7th Ave South, Birmingham, AL 35233 USA
来源
FEBS OPEN BIO | 2021年 / 11卷 / 10期
基金
美国国家卫生研究院;
关键词
exosome; extracellular vesicles; inflammation; microRNA; resilience; social defeat stress; BLOOD MONONUCLEAR-CELLS; DEFEAT STRESS; INFLAMMATORY RESPONSE; EMERGING ROLES; C57BL/6J MICE; DEPRESSION; MICRORNA; EXOSOMES; SERUM; NEUROINFLAMMATION;
D O I
10.1002/2211-5463.13204
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2678 / 2692
页数:15
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