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Deficiencies of microglia and TNF alpha in the mPFC-mediated cognitive inflexibility induced by social stress during adolescence
Zhang, Yu1,2,3; Xu, Hang1,2; Zhang, Fan1,2; Shao, Feng4; Ellenbroek, Bart5; Wang, Jiesi1; Wang, Weiwen1,2
First AuthorYu Zhang
2019-07-01
Source PublicationBRAIN BEHAVIOR AND IMMUNITY
Correspondent Emailwangjs@psych.ac.cn (j. wang) ; wangww@psych.ac.cn (w. wang)
ISSN0889-1591
Subtypearticle
Volume79Pages:256-266
Contribution Rank1
Abstract

The crucial roles played by microglia and their release of cytokines in the regulation of brain maturation are increasingly being recognized. Adolescence is a unique period characterized by continued brain maturation, especially in the area of the prefrontal cortex. Our previous studies showed that adolescent social stress induced impairment in extradimensional set-shifting (EDS), a core component of cognitive flexibility mediated by the medial prefrontal cortex (mPFC) in adult mice. The present study further determined the role of microglia and the inflammatory cytokine tumor necrosis factor alpha (TNF alpha) in cognitive dysfunction. Accompanied by a deficit in EDS in adulthood, previously stressed mice showed significant reductions in the expression of the microglial molecular biomarker Iba1, cell numbers, and the levels of TNF alpha mRNA and protein in the mPFC. Pharmacological inhibition of TNF alpha signaling by direct injection of a neutralizer into the mPFC also specifically impaired EDS performance. Moreover, the cognitive and immune alterations in previously stressed adult mice were ameliorated by both acute LPS and chronic antidepressant treatment. Together, our data suggest that microglia and TNF alpha play important roles in cognitive flexibility and can provide attractive therapeutic targets for the treatment of cognitive deficits in psychiatric disorders.

KeywordAdolescent social stress Medial prefrontal cortex (mPFC) Microglia Tumor necrosis factor alpha (TNF alpha) Set-shifting
DOI10.1016/j.bbi.2019.02.010
Indexed BySCI
Language英语
Funding OrganizationNational Natural Science Foundation of China ; Chinese Academy of Sciences ; CAS Key Laboratory of Mental Health, Institute of Psychology
Funding ProjectNational Natural Science Foundation of China[31771217] ; National Natural Science Foundation of China[81471122] ; National Natural Science Foundation of China[31470988] ; Chinese Academy of Sciences[KJZD-EW-L04] ; CAS Key Laboratory of Mental Health, Institute of Psychology
WOS Research AreaImmunology ; Neurosciences & Neurology ; Psychiatry
WOS SubjectImmunology ; Neurosciences ; Psychiatry
WOS IDWOS:000474328400032
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
WOS KeywordNECROSIS-FACTOR-ALPHA ; PREFRONTAL CORTEX ; DEPRESSION ; ACTIVATION ; BEHAVIOR ; MICE ; HIPPOCAMPUS ; DYSFUNCTION ; IMPAIRMENT ; RECEPTORS
Citation statistics
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/29511
Collection中国科学院心理健康重点实验室
Corresponding AuthorWang, Jiesi; Wang, Weiwen
Affiliation1.Inst Psychol, CAS Key Lab Mental Hlth, 16 Lincui Rd, Beijing 100101, Peoples R China
2.Univ Chinese Acad Sci, Dept Psychol, Beijing, Peoples R China
3.Binzhou Med Univ, Sch Nursing, Yantai, Peoples R China
4.Peking Univ, Beijing Key Lab Behav & Mental Hlth, Sch Psychol & Cognit Sci, Beijing, Peoples R China
5.Victoria Univ Wellington, Sch Psychol, Wellington 6012, New Zealand
Recommended Citation
GB/T 7714
Zhang, Yu,Xu, Hang,Zhang, Fan,et al. Deficiencies of microglia and TNF alpha in the mPFC-mediated cognitive inflexibility induced by social stress during adolescence[J]. BRAIN BEHAVIOR AND IMMUNITY,2019,79:256-266.
APA Zhang, Yu.,Xu, Hang.,Zhang, Fan.,Shao, Feng.,Ellenbroek, Bart.,...&Wang, Weiwen.(2019).Deficiencies of microglia and TNF alpha in the mPFC-mediated cognitive inflexibility induced by social stress during adolescence.BRAIN BEHAVIOR AND IMMUNITY,79,256-266.
MLA Zhang, Yu,et al."Deficiencies of microglia and TNF alpha in the mPFC-mediated cognitive inflexibility induced by social stress during adolescence".BRAIN BEHAVIOR AND IMMUNITY 79(2019):256-266.
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