Wang, Jiaxin;
Gao, Shuaixin;
Fu, Su;
Li, Yawei;
Su, Li;
Li, Xiaoman;
Wu, Guanghao;
... Wan, You; + view all
(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.
Preview |
Text
1-s2.0-S0889159124007463-main.pdf - Published Version Download (30MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Irisin reprograms microglia through activation of STAT6 and prevents cognitive dysfunction after surgery in mice |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.bbi.2024.12.019 |
| Publisher version: | https://doi.org/10.1016/j.bbi.2024.12.019 |
| Language: | English |
| Additional information: | 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/). |
| Keywords: | Anesthesia; Surgery; Dementia; Postoperative cognitive dysfunction (POCD); Irisin; Microglia; Hippocampus; Neuroinflammation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10203970 |
Loading...
Loading...Loading...Loading...Archive Staff Only
 |
View Item |
