中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Tofacitinib prevents depressive-like behaviors through decreased hippocampal microgliosis and increased BDNF levels in both LPS-induced and CSDS-induced mice

文献类型：期刊论文

作者Gao, Ya-nan4,5; Pan, Kai-jun4,5; Zhang, Yong-mei2,3,4; Qi, Ying-bei2,3,4; Chen, Wen-gang4,5; Zhou, Ting2,4; Zong, Hai-chao2,4; Guo, Hao-ran2,4; Zhao, Jin-wen2,4; Liu, Xing-chen2,4
刊名ACTA PHARMACOLOGICA SINICA
出版日期2024-09-30
页码13
关键词tofacitinib depression JAK-STAT pathway microgliosis synaptic defects
ISSN号1671-4083
DOI10.1038/s41401-024-01384-8
通讯作者Zang, Yi(yzang@lglab.ac.cn) ; Li, Jia(jli@simm.ac.cn)
英文摘要Depressive disorders are a global mental health challenge that is closely linked to inflammation, especially in the post-COVID-19 era. The JAK-STAT pathway, which is primarily associated with inflammatory responses, is not fully characterized in the context of depressive disorders. Recently, a phase 3 retrospective cohort analysis heightened that the marketed JAK inhibitor tofacitinib is beyond immune diseases and has potential for preventing mood disorders. Inspired by these clinical facts, we investigated the role of the JAK-STAT signaling pathway in depression and comprehensively assessed the antidepressant effect of tofacitinib. We found that aberrant activation of the JAK-STAT pathway is highly conserved in the hippocampus of classical depressive mouse models: LPS-induced and chronic social defeat stress (CSDS)-induced depressive mice. Mechanistically, the JAK-STAT pathway mediates proinflammatory cytokine production and microgliosis, leading to synaptic defects in the hippocampus of both depressive models. Remarkably, the JAK inhibitor tofacitinib effectively reverses these phenomena, contributing to its antidepressant effect. These findings indicate that the JAK/STAT pathway could be implicated in depressive disorders, and suggest that the JAK inhibitor tofacitinib has a potential translational implication for preventing mood disorders far beyond its current indications.
WOS关键词MAJOR DEPRESSION ; KINASE INHIBITOR ; DOUBLE-BLIND ; SYMPTOMS ; STRESS ; INFLAMMATION ; PSORIASIS ; MOOD
资助项目National Natural Science Foundation of China[82001572] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program[81971265] ; Shanghai Commission of Science and Technology[2018ZX09711002-007-002] ; Shanghai Science and Technology Development Funds (Shanghai Commission of Science and Technology)[2021000003] ; [19JC1416300]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001325456200003
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/313675]  
专题新药研究国家重点实验室
通讯作者Zang, Yi; Li, Jia
作者单位1.Lingang Lab, Shanghai 200120, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
4.Chinese Acad Sci, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
5.China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, Nanjing 210009, Peoples R China
推荐引用方式
GB/T 7714		 Gao, Ya-nan,Pan, Kai-jun,Zhang, Yong-mei,et al. Tofacitinib prevents depressive-like behaviors through decreased hippocampal microgliosis and increased BDNF levels in both LPS-induced and CSDS-induced mice[J]. ACTA PHARMACOLOGICA SINICA,2024:13.
APA Gao, Ya-nan.,Pan, Kai-jun.,Zhang, Yong-mei.,Qi, Ying-bei.,Chen, Wen-gang.,...&Li, Jia.(2024).Tofacitinib prevents depressive-like behaviors through decreased hippocampal microgliosis and increased BDNF levels in both LPS-induced and CSDS-induced mice.ACTA PHARMACOLOGICA SINICA,13.
MLA Gao, Ya-nan,et al."Tofacitinib prevents depressive-like behaviors through decreased hippocampal microgliosis and increased BDNF levels in both LPS-induced and CSDS-induced mice".ACTA PHARMACOLOGICA SINICA (2024):13.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。