| First Author | Ding X | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 2030 |
| PubMed ID | 33795678 | Mgi Jnum | J:305272 |
| Mgi Id | MGI:6705903 | Doi | 10.1038/s41467-021-22301-1 |
| Citation | Ding X, et al. (2021) Loss of microglial SIRPalpha promotes synaptic pruning in preclinical models of neurodegeneration. Nat Commun 12(1):2030 |
| abstractText | Microglia play a key role in regulating synaptic remodeling in the central nervous system. Activation of classical complement pathway promotes microglia-mediated synaptic pruning during development and disease. CD47 protects synapses from excessive pruning during development, implicating microglial SIRPalpha, a CD47 receptor, in synaptic remodeling. However, the role of microglial SIRPalpha in synaptic pruning in disease remains unclear. Here, using conditional knock-out mice, we show that microglia-specific deletion of SIRPalpha results in decreased synaptic density. In human tissue, we observe that microglial SIRPalpha expression declines alongside the progression of Alzheimer's disease. To investigate the role of SIRPalpha in neurodegeneration, we modulate the expression of microglial SIRPalpha in mouse models of Alzheimer's disease. Loss of microglial SIRPalpha results in increased synaptic loss mediated by microglia engulfment and enhanced cognitive impairment. Together, these results suggest that microglial SIRPalpha regulates synaptic pruning in neurodegeneration. |
