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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
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| 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
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| 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 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | https://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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