CXCR2 modulates chronic pain comorbid depression in mice by regulating adult neurogenesis in the ventral dentate gyrus
文献类型：期刊论文
| 作者 | Li, Xiao-jie4,5,6; Wu, Shuo5,6; Liu, Zi-han2,3; Liu, An-an2,3; Peng, Hui-sheng5,6; Wang, Yu-jun1,2,3 ; Chen, Ye-xiang5; Liu, Jing-gen2,3,5,6; Xu, Chi5
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2025-02-19 |
| 页码 | 13 |
| 关键词 | chronic pain comorbid depression adult neurogenesis dentate gyrus CXCR2 Wnt3a/beta-catenin pathway |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-025-01496-9 |
| 通讯作者 | Chen, Ye-xiang(yexiangchen@zcmu.edu.cn) ; Liu, Jing-gen(jgliu@simm.ac.cn) ; Xu, Chi(xuchi@zcmu.edu.cn) |
| 英文摘要 | Research shows that chronic pain may induce depression-like behaviors through impairing adult hippocampal neurogenesis (AHN) in the ventral dentate gyrus (DG), whereas restoration of AHN may effectively alleviate depression. The C-X-C motif chemokine receptor 2 (CXCR2) is a chemokine receptor involved in various neural activities of the hippocampus including AHN. In this study we investigated the role of CXCR2 of neural stem cells (NSCs) in the ventral DG in regulating both AHN and depression-like behaviors of mice with chronic neuropathic pain. Chronic neuropathic pain was induced in mice by the spared nerve injury (SNI) surgery; mechanical allodynia and depression-like behaviors were monitored, then mouse DG was collected for analysis. We observed that chronic neuropathic pain significantly decreased the number of immature neurons in the ventral DG by inhibiting the neuronal differentiation of NSCs; specific overexpression of CXCR2 in NSCs by injecting the adeno-associated virus (AAV) into the DG restored adult neurogenesis accompanied by alleviated depression-like behaviors in SNI mice. In contrast, the knockdown of CXCR2 in hippocampal NSCs of naive mice was sufficient to inhibit adult neurogenesis, inducing depression-like behaviors. Moreover, we found that the Wnt3a/beta-catenin pathway was downregulated in the ventral DG of SNI mice, which was restored after CXCR2 overexpression or infusing a CXCR2 agonist CXCL1 into the ventral DG. We conclude that CXCR2 expressed in hippocampal NSCs is crucial for regulating adult neurogenesis and chronic pain-induced depression-like behavior, thus representing a new target for the treatment of chronic pain comorbid depression. |
| WOS关键词 | HIPPOCAMPAL NEUROGENESIS ; NEURAL STEM ; DIFFERENTIATION ; IMPAIRMENT ; CHEMOKINES ; PRECURSORS ; MODEL |
| 资助项目 | Public Platform of Medical Research Center, Academy of Chinese Medical Science, Zhejiang Chinese Medical University ; Zhejiang Provincial Medical and Health Program[2025KY985] ; Zhejiang Provincial Natural Science Foundation of China[LY22H270004] ; Zhejiang Chinese Medical University[2022FSYYZZ11] ; National Natural Science Foundation of China[82030112] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001425314100001 |
| 出版者 | NATURE PUBL GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316275]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Chen, Ye-xiang; Liu, Jing-gen; Xu, Chi |
| 作者单位 | 1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 4.Wuhan Hankou Hosp, Dept Rehabil Hlth, Wuhan 430000, Peoples R China 5.Zhejiang Chinese Med Univ, Dept Neurobiol & Acupuncture Res, Key Lab Acupuncture & Neurol Zhejiang Prov, Affiliated Hosp 3, Hangzhou 310061, Peoples R China 6.Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou 310053, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Xiao-jie,Wu, Shuo,Liu, Zi-han,et al. CXCR2 modulates chronic pain comorbid depression in mice by regulating adult neurogenesis in the ventral dentate gyrus[J]. ACTA PHARMACOLOGICA SINICA,2025:13. |
| APA | Li, Xiao-jie.,Wu, Shuo.,Liu, Zi-han.,Liu, An-an.,Peng, Hui-sheng.,...&Xu, Chi.(2025).CXCR2 modulates chronic pain comorbid depression in mice by regulating adult neurogenesis in the ventral dentate gyrus.ACTA PHARMACOLOGICA SINICA,13. |
| MLA | Li, Xiao-jie,et al."CXCR2 modulates chronic pain comorbid depression in mice by regulating adult neurogenesis in the ventral dentate gyrus".ACTA PHARMACOLOGICA SINICA (2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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