TY  - JOUR
TI  - Irisin reprograms microglia through activation of STAT6 and prevents cognitive dysfunction after surgery in mice
EP  - 91
AV  - public
Y1  - 2025/03//
KW  - Anesthesia; Surgery; 
Dementia; Postoperative cognitive dysfunction (POCD); 
Irisin; Microglia; 
Hippocampus; 
Neuroinflammation
ID  - discovery10203970
N2  - 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 ?V?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.
PB  - ACADEMIC PRESS INC ELSEVIER SCIENCE
N1  - 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/).
SP  - 68
VL  - 125
JF  - Brain, Behavior, and Immunity
A1  - Wang, Jiaxin
A1  - Gao, Shuaixin
A1  - Fu, Su
A1  - Li, Yawei
A1  - Su, Li
A1  - Li, Xiaoman
A1  - Wu, Guanghao
A1  - Jiangi, Jiankuo
A1  - Zhao, Zifang
A1  - Yang, Chaojuan
A1  - Wang, Xiaoyi
A1  - Cui, Kun
A1  - Sun, Xiaoyan
A1  - Qi, Xuetao
A1  - Wang, Cheng
A1  - Sun, Haojie
A1  - Shao, Shan
A1  - Tian, Yue
A1  - Gong, Tingting
A1  - Luo, Jianyuan
A1  - Zheng, Jie
A1  - Cui, Shuang
A1  - Liao, Feifei
A1  - Liu, Fengyu
A1  - Wang, Dongxin
A1  - Wong, Catherine CL
A1  - Yi, Ming
A1  - Wan, You
SN  - 0889-1591
UR  - https://doi.org/10.1016/j.bbi.2024.12.019
ER  -