Fig. 5

Overexpression of STAT3 ameliorates P301L-induced synaptic impairments and memory deficits. AAV-P301L-hTau-eGFP with or without AAV-STAT3 were stereotaxically injected into hippocampal CA3 of 2-month-old C57 mice. Learning and memory ability and synaptic plasticity were assessed 1 month later. Upregulation of STAT3 was confirmed by Western blotting (a) and immunofluorescent staining (b). c Upregulation of STAT3 ameliorated P301L-induced spatial learning deficits shown by the decreased escape latency during 6 consecutive days training in the Morris water maze (MWM) test. Two-way repeated measures analysis of variance (ANOVA) followed by the Bonferroni’s post hoc test, P301L vs. Ctrl [day 3] p = 0.013, [day 4] p = 0.034, [day 5] p = 0.003; STAT3 vs. Ctrl [day 1] p = 0.016; P301L + STAT3 vs. P301L [day 2] p = 0.032, [day 4] p < 0.001, [day 5] p = 0.007, [day 6] p = 0.043. NCtrl/STAT3/P301L/P301L + STAT3 = 11/9/9/9. Upregulation of STAT3 ameliorated hTau-induced spatial memory deficits as shown by the representative swimming trace (d), the decreased latency to reach the platform quadrant (e), the increased time spent in the target quadrant (f), and crossing times in the platform site (g) measured at day 7 by removing the platform in the MWM test; no motor dysfunction was seen (h). Two-way analysis of variance (ANOVA) followed by the Bonferroni’s post hoc test. e **p = 0.005, ##p = 0.005; f **p = 0.007, ***p < 0.001, ###p < 0.001; g **p = 0.003, ###p < 0.001. NCtrl/STAT3/P301L/P301L + STAT3 = 11/9/9/9. i Upregulation of STAT3 ameliorated P301L-induced cognitive impairment as shown by the increased time spent in exploring the new novel object measured at 24 h. Two-way analysis of variance (ANOVA) followed by the Bonferroni’s post hoc test. ***p < 0.001, ##p = 0.004; NCtrl/STAT3/P301L/P301L + STAT3 = 11/9/9/9. j, k Upregulation of STAT3 ameliorated P301L-induced contextual memory deficits measured at 24 h. Two-way analysis of variance (ANOVA) followed by the Bonferroni’s post hoc test. **p = 0.006; NCtrl/STAT3/P301L/P301L + STAT3 = 11/9/9/9. Overexpression of STAT3 restored slopes of field excitatory postsynaptic potentials (fEPSP (l)) recorded in hippocampal CA3, with quantitative analysis thereof (m). Two-way analysis of variance (ANOVA) followed by the Bonferroni’s post hoc test. *p = 0.03, #p = 0.012; n = 6–8 slices from 4 mice for each group. n, o Overexpression of STAT3 restored the density of dendritic spine detected by Golgi staining. Representative image (n) and quantitative analysis (o). Scale bar, 5 μm. Two-way analysis of variance (ANOVA) followed by the Bonferroni’s post hoc test. **p = 0.002, #p = 0.039; n = at least 22 neurons from 6 mice per group. Data were presented as mean ± SEM