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Inhibition of JNK ameliorates depressive-like behaviors and reduces the activation of pro-inflammatory cytokines and the phosphorylation of glucocorticoid receptors at serine 246 induced by neuroinflammation
Zhang, Juntao1,2; Lin, Wenjuan1,2; Tang, Mingming1,3; Zhao, Yawei1,2; Zhang, Ke1,2; Wang, Xiaqing1,2; Li, Yingcong1
Corresponding AuthorLin, Wenjuan(linwj@psych.ac.cn)
AbstractDepression is associated with immune dysregulation and the aberrant activity of the hypothalamic-pituitary-adrenal (HPA) axis. However, the neurobiological molecular mechanisms underlying these associations remain unclear. c-Jun amino-terminal kinase (JNK), an important modulator in inflammation and stress responses, is often critically implicated in the development of central nervous system diseases. However, whether and how JNK mediates neuroinflammation-induced depression remains largely unknown. In this study, we investigated the role of JNK in depressive-like behaviors induced by central lipopolysaccharide (LPS) infusion. The results showed that LPS infusion led to depressive-like behaviors, accompanied by increased proinflammatory cytokine expression, increased JNK activation, and upregulated glucocorticoid receptor (GR) phosphorylation at serine 246 (pGR-Ser(246)) in the habenula (Hb), amygdala (Amyg) and medial prefrontal cortex (mPFC). Treatment with SP600125, a known JNK inhibitor, prevented the LPS-induced hyper-activation of JNK and alleviated depressive-like behaviors. Moreover, LPS-induced increases in the expression levels of TNF-alpha, IL-1 beta and pGR-Ser(246) in these brain regions were reduced when the rats were treated with SP600125. Our results show, for the first time, that JNK activities in the Hb, Amyg, and mPFC are involved in the modulation of neuroinflammation-induced depression and participate in the regulation of the expression of proinflammatory cytokines and GR phosphorylation, which are pathological factors associated with depression. Our findings provide new insights into the mechanism of neuroinflammation-associated depression and suggest that the JNK pathway may be a potential target for treating inflammation-related depression.
KeywordNeuroinflammation Depressive-like behavior JNK Proinflammatory cytokines Glucocorticoid receptor
2020-03-01
Language英语
DOI10.1016/j.psyneuen.2019.104580
Source PublicationPSYCHONEUROENDOCRINOLOGY
ISSN0306-4530
Volume113Pages:10
Indexed BySCI
Funding ProjectNational Natural Science Foundation of China[31170987] ; National Natural Science Foundation of China[31440045] ; CAS Key Laboratory of Mental Health, Institute of Psychology[KLMH2019K04]
PublisherPERGAMON-ELSEVIER SCIENCE LTD
WOS KeywordCORTICOSTEROID RECEPTORS ; ACUTE STRESS ; BRAIN ; KINASES ; NEUROBIOLOGY ; NUCLEAR ; PATHWAY ; TARGET ; MODEL
WOS Research AreaEndocrinology & Metabolism ; Neurosciences & Neurology ; Psychiatry
WOS SubjectEndocrinology & Metabolism ; Neurosciences ; Psychiatry
WOS IDWOS:000525937600014
Citation statistics
Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/31596
Collection中国科学院心理健康重点实验室
Corresponding AuthorLin, Wenjuan
Affiliation1.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
2.Univ Chinese Acad Sci, Dept Psychol, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China
First Author AffilicationKey Laboratory of Mental Health, CAS
Corresponding Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
Zhang, Juntao,Lin, Wenjuan,Tang, Mingming,et al. Inhibition of JNK ameliorates depressive-like behaviors and reduces the activation of pro-inflammatory cytokines and the phosphorylation of glucocorticoid receptors at serine 246 induced by neuroinflammation[J]. PSYCHONEUROENDOCRINOLOGY,2020,113:10.
APA Zhang, Juntao.,Lin, Wenjuan.,Tang, Mingming.,Zhao, Yawei.,Zhang, Ke.,...&Li, Yingcong.(2020).Inhibition of JNK ameliorates depressive-like behaviors and reduces the activation of pro-inflammatory cytokines and the phosphorylation of glucocorticoid receptors at serine 246 induced by neuroinflammation.PSYCHONEUROENDOCRINOLOGY,113,10.
MLA Zhang, Juntao,et al."Inhibition of JNK ameliorates depressive-like behaviors and reduces the activation of pro-inflammatory cytokines and the phosphorylation of glucocorticoid receptors at serine 246 induced by neuroinflammation".PSYCHONEUROENDOCRINOLOGY 113(2020):10.
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