Astroglial kappa opioid receptor-mediated reduction of glutamate exchanger xCT in the prelimbic cortex underlies chronic stress-induced depressive-like behaviors
文献类型：期刊论文
| 作者 | Chen, Yexiang1,3,4; Guo, Liu-Bin1,4,5; Zan, Gui-Ying1,4; Xu, Chi3; Yao, Song-Yu6; Wu, Shuo7; Jiang, Xingcong7; Liu, Zihan1,2,4; Long, Jian-Dong1,4; Liu, Boyu3,7 |
| 刊名 | MOLECULAR PSYCHIATRY
 |
| 出版日期 | 2025-12-24 |
| 页码 | 19 |
| ISSN号 | 1359-4184 |
| DOI | 10.1038/s41380-025-03441-y |
| 英文摘要 | Multiple lines of evidence, including clinical and preclinical, associate depression with dysregulated glutamate homeostasis in the central nervous system. The astrocyte-enriched cysteine/glutamate antiporter, xCT, plays a pivotal role in maintaining this homeostasis, and its dysfunction is linked to depressive-like behaviors induced by chronic stress. However, the exact mechanism through which chronic stress results in xCT dysfunction remains poorly understood. In this study, we demonstrate that chronic social defeat stress (CSDS) downregulates xCT expression in the prelimbic cortex (PL), a key cortical region involved in the aetiology of depression, through astroglial kappa opioid receptor (KOR)-dependent, p38 MAPK-mediated upregulation of miR-3084-5p expression, which in turn downregulates xCT expression by inhibiting mRNA that encodes xCT. Knockdown of KORs as well as overexpression of xCT in the PL astrocytes significantly attenuates CSDS-induced depressive-like behaviors. Blockade of p38 MAPK activity or suppression of miR-3084-5p function restores xCT expression and alleviates depressive-like behaviors. Together, this study reveals a novel mechanism by which chronic stress deregulates glutamate homeostasis and consequently results in depression. |
| WOS关键词 | SOCIAL DEFEAT STRESS ; ANTIPORTER SYSTEM X(C)(-) ; PREFRONTAL CORTEX ; EXTRACELLULAR GLUTAMATE ; ANTERIOR CINGULATE ; N-ACETYLCYSTEINE ; P38 MAPK ; TRANSPORTER ; ACTIVATION ; ASTROCYTES |
| 资助项目 | Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission)[23ZR1474900] ; National Natural Science Foundation of China (National Science Foundation of China)[82030112] ; National Natural Science Foundation of China (National Science Foundation of China)[82273904] ; Taishan Scholar Foundation of Shandong Province[SYS202205] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Neurosciences & Neurology ; Psychiatry |
| 语种 | 英语 |
| WOS记录号 | WOS:001645236400001 |
| 出版者 | SPRINGERNATURE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322420]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Shao, Xiaomei; Fang, Jianqiao; Liu, Jing-Gen; Wang, Yu-Jun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China 3.Zhejiang Chinese Med Univ, Clin Med Coll 3, Dept Neurobiol & Acupuncture Res, Key Lab Acupuncture & Neurobiol Zhejiang Prov, Hangzhou 310053, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Peoples R China 6.Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Peoples R China 7.Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Key Lab Neuropharmacol & Translat Med Zhejiang Pro, Hangzhou 310053, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Yexiang,Guo, Liu-Bin,Zan, Gui-Ying,et al. Astroglial kappa opioid receptor-mediated reduction of glutamate exchanger xCT in the prelimbic cortex underlies chronic stress-induced depressive-like behaviors[J]. MOLECULAR PSYCHIATRY,2025:19. |
| APA | Chen, Yexiang.,Guo, Liu-Bin.,Zan, Gui-Ying.,Xu, Chi.,Yao, Song-Yu.,...&Wang, Yu-Jun.(2025).Astroglial kappa opioid receptor-mediated reduction of glutamate exchanger xCT in the prelimbic cortex underlies chronic stress-induced depressive-like behaviors.MOLECULAR PSYCHIATRY,19. |
| MLA | Chen, Yexiang,et al."Astroglial kappa opioid receptor-mediated reduction of glutamate exchanger xCT in the prelimbic cortex underlies chronic stress-induced depressive-like behaviors".MOLECULAR PSYCHIATRY (2025):19. |
入库方式： OAI收割
来源：上海药物研究所
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