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Fig. 6 | Translational Neurodegeneration

Fig. 6

From: p85S6K sustains synaptic GluA1 to ameliorate cognitive deficits in Alzheimer’s disease

Fig. 6

Overexpression of p85S6K ameliorates cognitive decline and spine deficits in AD mice. a–f Morris water maze was carried out to assess spatial learning and memory. a Latency of WT and APP/PS1 mice to locate the hidden platform in the training period. F(1, 39) = 97.50, P < 0.0001 for genotype effect, F(1, 39) = 14.48, P = 0.0005 for p85S6K overexpression effect. b The average speed of WT and APP/PS1 mice in the training period. c The time spent in the target quadrant in the probe test. F(1, 39) = 6.731, P = 0.0133 for genotype effect, F(1, 39) = 9.915, P = 0.0013 for p85S6K overexpression effect. d The average speed of WT and APP/PS1 mice in the probe test. e The number of platform crossings of WT and APP/PS1 mice in the probe test. F(1, 39) = 4.522, P = 0.0398 for genotype effect, F(1, 39) = 7.984, P = 0.0074 for p85S6K overexpression effect. f Representative swimming trajectories in the probe test. The green circle represented the location of the hidden platform. n = 11 mice for WT-Ctl, WT-p85S6K OE, and APP/PS1-Ctl groups; n = 10 for the APP/PS1-p85S6K OE group. g, h The expression levels of p-Ser845 GluA1 and total GluA1 in the hippocampus after injection of AAVs expressing p85S6K or control AAVs. n = 5 mice per group. Left panel in h: F(1, 16) = 4.731, P = 0.0450 for genotype effect, F(1, 16) = 5.540, P = 0.0317 for p85S6K overexpression effect; right panel in h: F(1, 16) = 6.906, P = 0.0183 for genotype effect, F(1, 16) = 0.1139, P = 0.7401 for p85S6K overexpression effect. i, j Spine density in the hippocampus of WT and APP/PS1 mice after overexpression of p85S6K. Scale bars, 200 μm (left panel) and 1 μm (right panel). n = 9 slices from 4 mice per group. F(1, 32) = 14.97, P = 0.0005 for genotype effect, F(1, 32) = 16.22, P = 0.0003 for p85S6K overexpression effect. Data are presented as mean ± SEM. Three-way ANOVA (a, b) or two-way ANOVA (c, d, e, h, j) followed by Tukey's or Bonferroni's test. *P < 0.05, **P < 0.01, ****P < 0.0001.  Ctl control, i.e., mice injected with control AAVs. OE overexpression

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