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 m...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.展开更多
基金supported by grants from the Guangdong Basic and Applied Basic Research Foundation(2021A1515110912)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017)Shenzhen Key Laboratory of Translational Research for Brain Diseases(ZDSYS20200828154800001).
文摘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.
