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

doi:10.1016/j.psyneuen.2019.104580

	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, Juntao 1,2; Lin, Wenjuan1,2 ; Tang, Mingming 1,3; Zhao, Yawei 1,2; Zhang, Ke 1,2; Wang, Xiaqing 1,2; Li, Yingcong1
通讯作者	Lin, Wenjuan(linwj@psych.ac.cn)
摘要	Depression 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.
关键词	Neuroinflammation Depressive-like behavior JNK Proinflammatory cytokines Glucocorticoid receptor
	2020-03-01
语种	英语
DOI	10.1016/j.psyneuen.2019.104580
发表期刊	PSYCHONEUROENDOCRINOLOGY
ISSN	0306-4530
卷号	113 页码:10
收录类别	SCI
资助项目	National Natural Science Foundation of China[31170987] ; National Natural Science Foundation of China[31440045] ; CAS Key Laboratory of Mental Health, Institute of Psychology[KLMH2019K04]
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS关键词	CORTICOSTEROID RECEPTORS ; ACUTE STRESS ; BRAIN ; KINASES ; NEUROBIOLOGY ; NUCLEAR ; PATHWAY ; TARGET ; MODEL
WOS研究方向	Endocrinology & Metabolism ; Neurosciences & Neurology ; Psychiatry
WOS类目	Endocrinology & Metabolism ; Neurosciences ; Psychiatry
WOS记录号	WOS:000525937600014
资助机构	National Natural Science Foundation of China ; CAS Key Laboratory of Mental Health, Institute of Psychology
引用统计	被引频次：26[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.psych.ac.cn/handle/311026/31596
专题	中国科学院心理健康重点实验室
通讯作者	Lin, Wenjuan
作者单位	1.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
第一作者单位	中国科学院心理健康重点实验室
通讯作者单位	中国科学院心理健康重点实验室
推荐引用方式 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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