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. 2022 Jul 11;13(4):1293–1310. doi: 10.14336/AD.2022.0110

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copyright: © 2022 Xu et al.

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Figure 4. — Physical running alleviates synaptic deficits in the dorsal hippocampus of 3xTg-AD mice. (A-C) The levels of synaptic proteins including PSD-95, GluR1, and synaptophysin in hippocampal CA1. Representative bands from Ntg sedentary (1), Ntg running (2), 3xTg-AD sedentary (3), and 3xTg-AD running (4) mice at 7 months of age. The optical densities of bands corresponding to PSD-95, GluR1, and synaptophysin were normalized to respective protein levels of actin and expressed as % of Ntg sedentary controls. Whereas running wheel for 5 months upregulated the expressions of PSD-95 and synaptophysin, but not GluR1 in Ntg mice, running protected against the loss of all three measured proteins in 3xTg-AD mice (data were expressed as mean ± SEM, ** P < 0.01, * P < 0.05, n = 6). (D-J) Effects of running on PSD-95-ir puncta in area CA1. Representative confocal z-stack images in SR from Ntg sedentary (D), Ntg running (E), 3xTg-AD sedentary (F), and 3xTg-AD running (G) mice. Quantitative analysis of PSD-95-ir puncta (H-J). Three-way ANOVA analysis (genotype × running × region) showed a significant genotype effect ( F_[1,60] = 121.2, P< 0.0001) and running effect ( F_[1,60] = 77.64, P< 0.0001) with genotype-by-running interaction ( F_[1,60] = 22.70, P< 0.0001). Tukey’s post hoc test, ** P < 0.01, * P < 0.05. n = 6 mice per group. SO: stratum oriens; SR: stratum radiatum; SLM: stratum lacunosum-moleculare. Scale bars: 4 µm in D-G.