Semaglutide promotes the transition of microglia from M1 to M2 type to reduce brain inflammation in APP/PS1/tau mice.

Autor: Wang ZJ; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi Province, PR China., Han WN; Department of Physiology, Puai Medical College (Medical College), Shaoyang University, Shaoyang, Hunan Province, PR China., Chai SF; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi Province, PR China., Li Y; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi Province, PR China., Fu CJ; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi Province, PR China., Wang CF; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi Province, PR China., Cai HY; Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, Shanxi Province, PR China., Li XY; Department of Neurology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Tongji Shanxi Hospital, Taiyuan, Shanxi Province, PR China., Wang X; Department of Psychiatry, First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi Province, PR China., Hölscher C; Henan Academy of Innovations in Medical Science, Brain Institute, Zhengzhou, Henan Province, PR China. Electronic address: c.holscher@hactcm.edu.cn., Wu MN; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi Province, PR China. Electronic address: wmna@163.com.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2024 Dec 17; Vol. 563, pp. 222-234. Date of Electronic Publication: 2024 Nov 14.
DOI: 10.1016/j.neuroscience.2024.11.022
Abstrakt: A growing number of studies show that the diabetes drug Semaglutide is neuroprotective in Alzheimer's disease (AD) animal models, but its mode of action is not fully understood. In order to explore the mechanism of Semaglutide, 7-month-old APP/PS1/tau transgenic (3xTg) mice and wild-type (WT) mice were randomly divided into four groups: control group (WT + PBS), AD model group (3xTg + PBS), Semaglutide control group (WT + Semaglutide) and Semaglutide treatment group (3xTg + Semaglutide). Semaglutide (25 nmol/kg) or PBS was administered intraperitoneally once every two days for 30 days, followed by behavioral and molecular experiments. The results show that Semaglutide can improve working memory and spatial reference memory of 3xTg-AD mice, promote the release of anti-inflammatory factors and inhibit the production of pro-inflammatory factors in the cortex and hippocampus, and reduce Aβ deposition in the hippocampal CA1 region of 3xTg mice. Semaglutide can inhibit the apoptosis of BV2 cells induced by Aβ1-42 in a dose-dependent manner and promote the transformation of microglia from M1 to M2, thereby exerting anti-inflammatory and neuroprotective effects. Therefore, we speculate that Semaglutide shows an anti-inflammatory effect by promoting the transformation of microglia from M1 to M2 type in the brain of 3xTg mice, and thus exerts a neuroprotective effect.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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