Effect Of Synaptic CD47 Molecular Deletion On The Pathological Process Of AD

CD47(Cluster of Differentiation 47)is an anti-phagocyte receptor with multiple signaling functions.CD47 is expressed in a variety of cells and transmits the "don’t eat me" signal to macrophages to prevent phagocytosis of macrophages.If the CD47 receptor of cells are down-regulated due to physiological or pathological reasons,they are more likely to be phagocytized and removed by macrophages.SIRPα(Signal regulatory protein α)is a regulatory glycoprotein of the signal regulatory protein family,which is mainly expressed in the cell membrane of myeloid cells,stem cells and neurons.SIRPα-CD47 signal pathway prevents phagocytosis by inhibiting the activation of macrophage integrin signal.Microglia are highly active phagocytes that permeate and reside in the brain to provide monitoring and clearance functions.Microglia play a key role in the pruning/clearance of neuronal synapses.If there is any disorder in this process,it will lead to abnormal behavior of mice in adulthood,resulting in social behavior disorders such as autism.During the early development of the nervous system,microglia SIRPα interacts with synaptic CD47 molecules to produce signals that inhibit microglia phagocytosis and protect synapses from over-elimination.However,the changes and role of related signals in synaptic pathologyrelated diseases have not been reported.The main purpose of this study is to discover the regulation mechanism of synaptic CD47 signal and to evaluate the effect of SIRPα-CD47 signal changes on synaptic pathology in AD animal model during the pathological process of Alzheimer’s disease.The results show that: 1.The expression of synaptic CD47 in neurons is regulated by neural activity;2.When the expression of CD47 in synapses decreased,the phagocytosis of microglia to synapses increased;3.In AD pathology,SIRPα-CD47 signal pathway is blocked due to the decrease of CD47 level of neuronal synapse,which aggravates synaptic loss and pathological process in AD animal model.In order to prove the synergistic effect of SIPRα and CD47 signal,we used SIPRα c KO mice model combined with ICV injection of Aβo.The results showed that the deletion of SIRPα in microglia weakened its ability to recognize synaptic CD47 molecules and increased synaptic elimination.The loss of SIPR αsignal can reproduce the over-elimination phenotype of synapses in CD47 knockout mice.These results suggest that the abnormality of SIRPα-CD47 signal is involved in the synaptic pathology of AD.To sum up,our results show that synaptic CD47 molecules can negatively regulate synaptic elimination by binding to SIRPα on microglia,which plays a key role in both physiological and pathological conditions of AD.