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Fig. 6 | Molecular Neurodegeneration

Fig. 6

From: VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice

Fig. 6

Chronic ICV administration of TLQP-21 reduces amyloid plaque load and restores expression of subsets of Alzheimer disease-associated microglial genes in 5xFAD male mice. a, Top: Western-blot and quantification of brain VGF protein expression in WT and 5xFAD mice, n = 4 male mice per group. Bottom: schematic representation of the intracerebroventricular infusion of TLQP-21 (or aCSF) performed on WT or 5xFAD mice at 3 months of age for 28 consecutive days. b, Left: Representative images of Aβ plaques (6E10, green) and surrounding microglia (IBA1, red) in hippocampi of 5xFAD male mice treated with TLQP-21 or aCSF. Scale bar = 200 μm. Right: Representative images of dystrophic neurites labelled with anti-LAMP1 (DAB immunohistochemistry) in the cortical areas of WT and 5xFAD mice treated with aCSF or TLQP-21. Scale bar = 500 μm. c, Quantification of the Aβ plaque area in brain regions (cerebral cortex, hippocampus CA1, and dentate gyrus + hilus), n = 4–5 male mice per group. 2 brain sections per animal were used for the analysis. d, Quantification of dystrophic neurite clusters illustrated in B, n = 5 male mice per group. 1 brain section per animal was used for analysis. e, Western blots from cortices of WT or 5xFAD male mice injected with aCSF and TLQP-21 using 6E10 antibody for human APP, n = 4–5 male mice per group. f, Percentage of spontaneous alternations between both arms of the maze, n = 11–12 male mice per group. g, Quantification of the area occupied by microglia in brain regions (cerebral cortex, hippocampus CA1, and dentate gyrus + hilus), n = 4–5 male mice per group. 1 brain section per animal was used for analysis. h, RT-qPCR analysis of microglial genes in the hippocampus of the 3 groups presented in (e), n = 4 male mice per group. Error bars represent means ± SEM. Statistical analyses were performed using a Student-t-test for A, C, D and F(*t). A One-Way ANOVA followed by a Tukey’s post-hoc test was used for G and H, *p < 0.05; **p < 0.01; ***p < 0.001, ****p < 0.0001

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