Authors
Dylan M Belmont-Rausch, Mette Q Ludwig, Marie A Bentsen, Stine N Hansen, Anna Secher, Dorte Holst, Jaime Moreno, Vivek Das, Kristoffer L Egerod, Anne-Mette Bjerregaard, Kristoffer Niss, Sarah Bau, Charles Pyke, Kevin Dalgaard, Myrte Merkestein, Franziska Wichern, Charlotte Thim Hansen, Joseph Polex-Wolf, Lotte Bjerre Knudsen, Tune H Pers
Published in
Nature communications. Volume 17. Issue 1. Jun 09, 2026. Epub Jun 09, 2026.
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise in preclinical models of neurodegeneration, with emerging evidence suggesting these effects may be driven by modulation of neuroinflammation. However, the cellular mechanisms underlying GLP-1RA effects on neuroinflammation remain poorly understood. Here we show, using a mouse model of lipopolysaccharide-induced neuroinflammation, how semaglutide coordinates cellular responses to resolve neuroinflammation. We find that semaglutide in male mice prevents brain infiltration of neutrophils, excessive cytokine release, and suppresses neuroinflammation-associated transcriptional signatures specifically in microglia, endothelial cells, and a subset of pericytes. Mechanistically, we identify a subset of Glp1r-expressing neurons in the dorsal vagal complex that, upon semaglutide treatment, regulate genes involved in anti-inflammatory signaling. Semaglutide-modulated pathways overlap with inflammatory signatures found in human neurodegenerative diseases, including Alzheimer's disease, suggesting broad relevance for conditions involving neuroinflammation. Together, these findings reveal how GLP-1R signaling in male mice orchestrates resolution of neuroinflammation through coordinated multi-cellular programs.
PMID:
42265098
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.
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