eprintid: 10203970 rev_number: 8 eprint_status: archive userid: 699 dir: disk0/10/20/39/70 datestamp: 2025-01-27 08:28:47 lastmod: 2025-01-27 08:31:34 status_changed: 2025-01-27 08:28:47 type: article metadata_visibility: show sword_depositor: 699 creators_name: Wang, Jiaxin creators_name: Gao, Shuaixin creators_name: Fu, Su creators_name: Li, Yawei creators_name: Su, Li creators_name: Li, Xiaoman creators_name: Wu, Guanghao creators_name: Jiangi, Jiankuo creators_name: Zhao, Zifang creators_name: Yang, Chaojuan creators_name: Wang, Xiaoyi creators_name: Cui, Kun creators_name: Sun, Xiaoyan creators_name: Qi, Xuetao creators_name: Wang, Cheng creators_name: Sun, Haojie creators_name: Shao, Shan creators_name: Tian, Yue creators_name: Gong, Tingting creators_name: Luo, Jianyuan creators_name: Zheng, Jie creators_name: Cui, Shuang creators_name: Liao, Feifei creators_name: Liu, Fengyu creators_name: Wang, Dongxin creators_name: Wong, Catherine CL creators_name: Yi, Ming creators_name: Wan, You title: Irisin reprograms microglia through activation of STAT6 and prevents cognitive dysfunction after surgery in mice ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D10 divisions: G10 keywords: Anesthesia; Surgery; Dementia; Postoperative cognitive dysfunction (POCD); Irisin; Microglia; Hippocampus; Neuroinflammation note: Copyright © 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). abstract: Postoperative cognitive dysfunction (POCD) is common in the aged population and associated with poor clinical outcomes. Irisin, an endogenous molecule that mediates the beneficial effects of exercise, has shown neuroprotective potential in several models of neurological diseases. Here we show that preoperative serum level of irisin is reduced in dementia patients over the age of 70. Comprehensive proteomics analysis reveals that deletion of irisin affects the nervous and immune systems, and reduces the expression of complement proteins. Systemically administered irisin penetrates the blood–brain barrier in mice, targets the microglial integrin αVβ5 receptor, activates signal transducer and activator of transcription 6 (STAT6), induces microglia reprogramming to the M2 phenotype, and improves immune microenvironment in LPS-induced neuroinflammatory mice. Finally, prophylactic administration of irisin prevents POCD-like behavior, particularly early cognitive dysfunction. Our findings provide new insights into the direct regulation of the immune microenvironment by irisin, and reveal that recombinant irisin holds great promise as a novel therapy for preventing POCD and other neuroinflammatory disorders. date: 2025-03 date_type: published publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE official_url: https://doi.org/10.1016/j.bbi.2024.12.019 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2344516 doi: 10.1016/j.bbi.2024.12.019 medium: Print-Electronic pii: S0889-1591(24)00746-3 lyricists_name: Sun, Haojie lyricists_id: HSUNB86 actors_name: Sun, Haojie actors_name: Harris, Jean actors_id: HSUNB86 actors_id: JAHAR68 actors_role: owner actors_role: impersonator funding_acknowledgements: 32,271,053 [National Natural Science Foundation of China]; 31,872,774 [National Natural Science Foundation of China]; 32,150,005 [National Natural Science Foundation of China]; 82,293,644 [National Natural Science Foundation of China]; 32,171,002 [National Natural Science Foundation of China]; 2022YFA0806000 [Ministry of Science and Technology of China]; 2023000CA0060 [Beijing Life Science Academy]; ZHYZ-2024-101 [Medical Innovation Center (Taizhou) of Peking University]; 7,242,086 [Beijing Natural Science Foundation]; 2022-12 M-1-004 [Clinical Research Operating Fund of Central High Level Hospitals, Medical and Scientific Innovation Project of the Chinese Academy of Medical Science]; [Research Funds from Health @InnoHK Program launched by the Innovation Technology Commission of the Hong Kong Special Administrative Region]; 2019BD007 [PKU-Baidu Fund]; 2020YFE0202200 [Training Program of the Big Science Strategy Plan]; 2017YFA0701302 [Peking University People's Hospital Scientific Research Development Funds RDX]; [National Key R&D Program of China]; 32,371,049; 2022-02 full_text_status: public publication: Brain, Behavior, and Immunity volume: 125 pagerange: 68-91 pages: 24 event_location: Netherlands issn: 0889-1591 citation: Wang, Jiaxin; Gao, Shuaixin; Fu, Su; Li, Yawei; Su, Li; Li, Xiaoman; Wu, Guanghao; ... Wan, You; + view all <#> Wang, Jiaxin; Gao, Shuaixin; Fu, Su; Li, Yawei; Su, Li; Li, Xiaoman; Wu, Guanghao; Jiangi, Jiankuo; Zhao, Zifang; Yang, Chaojuan; Wang, Xiaoyi; Cui, Kun; Sun, Xiaoyan; Qi, Xuetao; Wang, Cheng; Sun, Haojie; Shao, Shan; Tian, Yue; Gong, Tingting; Luo, Jianyuan; Zheng, Jie; Cui, Shuang; Liao, Feifei; Liu, Fengyu; Wang, Dongxin; Wong, Catherine CL; Yi, Ming; Wan, You; - view fewer <#> (2025) Irisin reprograms microglia through activation of STAT6 and prevents cognitive dysfunction after surgery in mice. Brain, Behavior, and Immunity , 125 pp. 68-91. 10.1016/j.bbi.2024.12.019 <https://doi.org/10.1016/j.bbi.2024.12.019>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10203970/1/1-s2.0-S0889159124007463-main.pdf