@article{discovery10203970,
       publisher = {ACADEMIC PRESS INC ELSEVIER SCIENCE},
         journal = {Brain, Behavior, and Immunity},
           pages = {68--91},
            note = {Copyright {\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/).},
          volume = {125},
           title = {Irisin reprograms microglia through activation of STAT6 and prevents cognitive dysfunction after surgery in mice},
            year = {2025},
           month = {March},
          author = {Wang, Jiaxin and Gao, Shuaixin and Fu, Su and Li, Yawei and Su, Li and Li, Xiaoman and Wu, Guanghao and Jiangi, Jiankuo and Zhao, Zifang and Yang, Chaojuan and Wang, Xiaoyi and Cui, Kun and Sun, Xiaoyan and Qi, Xuetao and Wang, Cheng and Sun, Haojie and Shao, Shan and Tian, Yue and Gong, Tingting and Luo, Jianyuan and Zheng, Jie and Cui, Shuang and Liao, Feifei and Liu, Fengyu and Wang, Dongxin and Wong, Catherine CL and Yi, Ming and Wan, You},
        keywords = {Anesthesia; Surgery; 
Dementia; Postoperative cognitive dysfunction (POCD); 
Irisin; Microglia; 
Hippocampus; 
Neuroinflammation},
        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 {\ensuremath{\alpha}}V{\ensuremath{\beta}}5 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.},
            issn = {0889-1591},
             url = {https://doi.org/10.1016/j.bbi.2024.12.019}
}