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Effect of Toll-like receptor 4 on depressive-like behaviors induced by chronic social defeat stress
Zhang, Ke1,2; Lin, Wenjuan1; Zhang, Juntao1,2; Zhao, Yawei1,2; Wang, Xiaqing1,2; Zhao, Mei1,2
First AuthorZhang, Ke
Correspondent Emailzhaomei@psych.ac.cn ; linwj@psych. ac.cn
2020-01-16
Source PublicationBRAIN AND BEHAVIOR
ISSN2162-3279
Subtypearticle
Pages10
Contribution Rank1
Abstract

Introduction A growing body of evidence suggests that stress is an important factor in depression, and pro-inflammatory cytokines contribute to the occurrence and development of depression in both animal models and human patients. Toll-like receptor 4 (TLR4) has been shown to be a key innate immune pattern recognition receptor involved in the regulation of stress responses and inflammation. However, the exact effects of TLR4 on depressive-like behaviors induced by chronic social defeat stress (CSDS) are not known. Methods In this study, the effects of TLR4 on depressive-like behaviors were investigated in an animal model of depression induced by CSDS. The depressive-like behaviors were assessed by forced swimming test (FST), social interaction test (SIT), and light-dark box test (LDT). The protein expressions of TLR4 and tumor necrosis factor-alpha (TNF-alpha) in the hippocampus were measured using Western blotting. Results We found that CSDS increased TLR4 protein levels in the hippocampus and induced behavioral despair in FST, social avoidance in SIT, and anxiety-like behavior in LDT. Fluoxetine normalized the increased expression of TLR4 and reversed behavioral despair, social avoidance, as well as anxiety-like behavior induced by CSDS. However, directly blocking TLR4, by using either TLR4 inhibitor TAK-242 or knockout of TLR4, only inhibited behavioral despair, but not social avoidance or anxiety-like behavior induced by CSDS. Conclusions These results demonstrate a specific modulating role of TLR4 in behavioral despair induced by CSDS and suggest that TAK-242 may be a beneficial treatment for patients with behavioral despair.

Keywordbehavioral despair chronic social defeat stress depression inflammation TLR4
DOI10.1002/brb3.1525
Indexed BySCI
Language英语
Funding OrganizationNational Natural Science Foundation of China ; Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences
Funding ProjectNational Natural Science Foundation of China[91132728] ; National Natural Science Foundation of China[31741062] ; Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences
WOS Research AreaBehavioral Sciences ; Neurosciences & Neurology
WOS SubjectBehavioral Sciences ; Neurosciences
WOS IDWOS:000507439300001
PublisherWILEY
WOS KeywordSIGNAL-TRANSDUCTION INHIBITOR ; INDUCED NEUROINFLAMMATION ; ANIMAL-MODEL ; TAK-242 ; MOUSE ; CYTOKINES ; NEUROGENESIS ; INFLAMMATION
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Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/30658
Collection中国科学院心理健康重点实验室
Corresponding AuthorLin, Wenjuan; Zhao, Mei
Affiliation1.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, 16 Lincui Rd, Beijing, Peoples R China
2.Univ Chinese Acad Sci, Dept Psychol, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Zhang, Ke,Lin, Wenjuan,Zhang, Juntao,et al. Effect of Toll-like receptor 4 on depressive-like behaviors induced by chronic social defeat stress[J]. BRAIN AND BEHAVIOR,2020:10.
APA Zhang, Ke,Lin, Wenjuan,Zhang, Juntao,Zhao, Yawei,Wang, Xiaqing,&Zhao, Mei.(2020).Effect of Toll-like receptor 4 on depressive-like behaviors induced by chronic social defeat stress.BRAIN AND BEHAVIOR,10.
MLA Zhang, Ke,et al."Effect of Toll-like receptor 4 on depressive-like behaviors induced by chronic social defeat stress".BRAIN AND BEHAVIOR (2020):10.
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