Fig. 7: Wild-type serum rescues synaptic loss and microglial branching complexity in APP/PS1 mice. | Molecular Psychiatry

Fig. 7: Wild-type serum rescues synaptic loss and microglial branching complexity in APP/PS1 mice.

From: VEGF-A in serum protects against memory impairment in APP/PS1 transgenic mice by blocking neutrophil infiltration

Fig. 7

Representative confocal images (A–D) and quantification (E) of synaptophysin and GluA1 in the CA1, CA3, and DG in the hippocampus of WT mice, APP/PS1 mice treated with AAV-Cdk5, and the controls. IR: immunoreactivity; Scale bar, 100 μm. F Western blot analysis of synaptic proteins including GluA1, PSD95, and synaptophysin in the hippocampus. Data are represented as the mean ± s.e.m.; one-way ANOVA and LSD multiple comparison tests, n = 4 mice per group (more than 10 image fields from 5 brain slices per animal were analyzed and averaged as a value); *p < 0.05; **p < 0.01, ns nonsignificant. G Schematic of the experiments in H–K. H Confocal images and 3D reconstruction of microglial processes (Cx3cr1-GFP) engulfing GluA1+ puncta, the percentage of engulfed puncta by microglia was assessed. Data are represented as the mean ± s.e.m.; one-way ANOVA and LSD multiple comparison tests, n = 5 mice per group (more than 34 microglia from 5 brain slices per animal were analyzed and averaged as a value); *p < 0.05; **p < 0.01. I Engulfed puncta distributed inside microglia, the distance is less than 0 μm from the microglial surface; and contacted puncta distributed outside microglia, but the distance is less than 0.25 μm from the microglial surface. Purple puncta were shown in I (below). J 3D reconstruction of microglial processes and GluA1+ puncta in WT mice, as well as Aβ plaques (blue) in APP/PS1 mice, and contacted GluA1 puncta (less than 0.25 μm) were analyzed (n = 25–44 cells from 7 mice). K Sholl analysis of 3D-reconstructed microglia (n = 14–21 cells from 3 mice per group). *p < 0.05; **p < 0.01. Scale bar: 1 μm in H, I; 5 μm in J, 10 μm in K. L Representative traces of mEPSCs in DG pyramidal neurons from wide-type mice, APP/PS1 mice, and APP/PS1 mice treated with AAV-Cdk5, Scale bar: 1 s, 20 pA. M Average frequencies of mEPSCs. N Average amplitudes of mEPSCs; Kolmogorov–Smirnov test; *p < 0.05; ***p < 0.001; n = 19 or 20 cells from 3 mice/group in M and N.

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