Fig. 4

Genetic P2X7R knockdown rescues UPS dysfunction associated with the AD’s mouse model, P301S mice. A Representative immunoblots of Nfr2, p-GSK3, total GSK3 (tGSK3), β1, and β5 protein levels in hippocampal homogenates from P301S and P301S;P2X7^−/− mice (n = 4–7 mice per genotype). Graphs show p-GSK3β, o β5, β1, and Nfr2 protein levels using -tubulin or tGSK3β signal for normalization purposes. The 100% value corresponds to p-GSK3β, β5, β1, and Nfr2 levels detected in the hippocampus of P301S mice. B Representative images of hippocampal slices from UbGFP mice and UbGFP;P301S mice stained with anti-GFP antibody. Scale bar: 200 μm. Inserts show magnification X2 of hippocampal CA3 area limited by square with discontinuous sides. Graph represents the quantification of GFP positive cells in CA3 area (n = 3 per genotype with at least 3 slices per mice). * P ≤ 0.05; ** P ≤ 0.01; using an unpaired two-tailed Student’s t-test. C Representative immunofluorescence images of hippocampal CA3 area stained with anti-NeuN antibody from WT, P301S, GSK-treated P301S, and P301S;P2X7^−/− mice. Scale bars 50 μm. Graphs show the quantification of the neuronal hippocampal cell identified as NeuN positive (n ≥ 3 mice per genotype and treatment and n ≥ 4 slices per mice). Data in bar graphs represent mean ± s.e.m. *p ≤ 0.05; using a one-way ANOVA followed by Tukey’s post hoc test