Fig. 4

Pharmacological inhibition of C5aR1 rescues VGlut1 loss and reduces synaptic engulfment by microglial cells in the Tg2576 mouse model of AD. A Representative confocal images and tridimensional reconstruction of individual microglial cells (Iba1: gray), pre-synapses (VGlut1: cyan) or internalized pre-synapses (VGlut1: yellow and arrowheads) and microglial lysosomes (CD68: red) in the CA3 hippocampal region of WT and Tg2576 treated with vehicle or PMX205 (A1–A4). Quantitative analysis of the number of pre-synapses internalized by microglial cells revealed a decrease in the synaptic phagocytosis by microglial cells in the Tg2576-PMX205 mice when compared to Tg2576-vehicle (A5). VGlut1 puncta quantification showed a strong reduction of pre-synapses in the Tg2576 mice when compared to WT mice, that was restored in the Tg2576 mice treated with PMX205 vs vehicle treated mice (A6). Data are shown as Mean ± SEM and normalized to control group (WT-vehicle). Statistical analysis used a 2-way ANOVA. Significance is indicated as *p < 0.05; and ****p < 0.0001. 15 individual microglial cells/mouse and n = 4–5 per group. Scale bar: A1–A4: 5 µm