Fig. 8: Inhibition of microglial SIRPα increased Aβo-induced synapse loss by promoting microglia-mediated synaptic elimination.
From: Loss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration
a Schematics of the experimental procedures, Cx3cr1CreERT2:SIRPαfl/fl (-TAM) mice are used as normal control. ICV intracerebroventricular, FC flow cytometry, TAM tamoxifen. b, c Representative confocal images (b) depict synaptic staining for presynaptic marker Synapsin I (red) and postsynaptic marker PSD95 (green) in cortex, Scale bars, 10 μm. Aβm, Aβ42 monomer; Aβo, Aβ42 oligomer. The histogram c displays the quantification of synaptic density in these mice. n = 5 mice/group (male, 3 months age), average of 6–8 fields from each mouse. One-way ANOVA, by Tukey’s multiple comparison test. d, e 3D reconstruction and surface rendering demonstrate larger volumes of PSD95+ puncta inside Iba-1+ microglia in cortex from SIRPα-cKO mice versus control mice after Aβo stimulation (2 μg/mouse), Grid line increments = 5 μm. n = 8 mice/group, average of 8–9 microglia from each mouse, two-tailed unpaired t test. f, g Flow cytometry analysis of synaptic material (PSD95+) engulfed by microglia in SIRPα-cKO or control mice after Aβo injection. n = 3 mice/group, average of three tests from each mouse, two-tailed unpaired t test. Data are mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001, NS not significant. Detailed statistical information was listed in Supplementary Statistical Data. Source data are provided as a Source Data file.
