Loss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration

• DOI: 10.1038/s41467-021-22301-1
• Publication Date: 2021-04-01T10:03:08Z
• Authors: Xin Ding; Jin Wang; Miaoxin Huang; Zhangpeng Chen; Jing Liu; Qipeng Zhang; Chenyu Zhang; Yang Xiang; Ke Zen; Liang Li
• Keywords: Synaptic Pruning

Abstract Microglia play a key role in regulating synaptic remodeling the central nervous system. Activation of classical complement pathway promotes microglia-mediated pruning during development and disease. CD47 protects synapses from excessive development, implicating microglial SIRPα, receptor, remodeling. However, SIRPα disease remains unclear. Here, using conditional knock-out mice, we show that microglia-specific deletion results decreased density. In human tissue, observe expression declines alongside progression Alzheimer’s To investigate neurodegeneration, modulate mouse models Loss increased loss mediated by microglia engulfment enhanced cognitive impairment. Together, these suggest regulates neurodegeneration.