Modulation of Ryanodine Receptors on Microglial Ramification, Migration, and Phagocytosis in an Alzheimer's Disease Mouse Model.
10.1007/s12264-025-01469-2
- Author:
Yulin OUYANG
1
;
Zihao CHEN
1
;
Qiang HUANG
1
;
Hai ZHANG
1
;
Haolin SONG
1
;
Xinnian WANG
1
;
Wenxiu DONG
1
;
Yong TANG
1
;
Najeebullah SHAH
2
;
Shimin SHUAI
2
;
Yang ZHAN
3
Author Information
1. Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
2. Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.
3. Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. yang.zhan@siat.ac.cn.
- Publication Type:Journal Article
- Keywords:
Alzheimer’s disease;
ER calcium signaling;
Microglia;
ORAI;
Ryanodine receptor
- MeSH:
Animals;
Microglia/pathology*;
Alzheimer Disease/pathology*;
Phagocytosis/drug effects*;
Ryanodine Receptor Calcium Release Channel/metabolism*;
Disease Models, Animal;
Mice;
Cell Movement/drug effects*;
Mice, Transgenic;
Calcium Signaling/physiology*;
Calcium/metabolism*;
Mice, Inbred C57BL;
Male;
Endoplasmic Reticulum/metabolism*
- From:
Neuroscience Bulletin
2025;41(11):2063-2077
- CountryChina
- Language:English
-
Abstract:
Microglial functions are linked to Ca2+ signaling, with endoplasmic reticulum (ER) calcium stores playing a crucial role. Microglial abnormality is a hallmark of Alzheimer's disease (AD), but how ER Ca2+ receptors regulate microglial functions under physiological and AD conditions remains unclear. We found reduced ryanodine receptor 2 (Ryr2) expression in microglia from an AD mouse model. Modulation of RyR2 using S107, a RyR-Calstabin stabilizer, blunted spontaneous Ca2+ transients in controls and normalized Ca2+ transients in AD mice. S107 enhanced ATP-induced migration and phagocytosis while reducing ramification in control microglia; however, these effects were absent in AD microglia. Our findings indicate that RyR2 stabilization promotes an activation state shift in control microglia, a mechanism impaired in AD. These results highlight the role of ER Ca2+ receptors in both homeostatic and AD microglia, providing insights into microglial Ca2+ malfunctions in AD.
