Fig. 4
Downregulation of STAT3 induced synaptic impairments and memory deficits in STAT3flox/flox mice. a, b AAV-Cre was stereotaxically injected into the hippocampal CA3 of 2-month-old STAT3flox/flox mice. One month later, downregulation of STAT3 was confirmed by Western blotting (a) and immunohistochemical staining (b). Two-tailed Student’s t test, p = 0.031, n = 3. c STAT3 knockdown induced spatial learning deficits during Morris water maze (MWM) training. Two-way repeated measures analysis of variance (ANOVA) followed by the Bonferroni’s post hoc test, [day 2] p = 0.018, [day 3] p = 0.001, [day 4] p = 0.003, [day 5] p = 0.013, [day 6] p = 0.014, nCtrl/CRE = 11/9. STAT3 knockdown induced spatial memory deficits shown by the increased escape latency to reach the platform quadrant (d), the decreased crossing time in the platform site (e), and time spent in the target quadrant (f) measured at day 7 by removal of the platform in MWM test; no motor dysfunction was seen (g). Two-tailed Student’s t test; d p = 0.029; e p = 0.033; f p = 0.003; nCtrl/CRE = 11/9. h STAT3 knockdown induced cognition impairment shown by the decreased time spent in exploring the new novel object. Two-tailed Student’s t test, p < 0.001, n = 8. i, j STAT3 knockdown impaired long-term memory as shown by the decreased freezing time measured in the fear conditioning test. Two-tailed Student’s t test, j p = 0.0037, n = 8. STAT3 knockdown decreased slopes of field excitatory postsynaptic potentials (fEPSP (k)) recorded in hippocampal CA3, and quantitative analysis (l). Two-tailed Student’s t test, p = 0.0013, n = 7–8 slices from 4 mice per group. m, n STAT3 knockdown decreased the density of dendritic spines detected by Golgi staining. Scale bar, 5 μm. Two-tailed Student’s t test, p < 0.001, n = at least 22 neurons were analyzed from 6 mice per group. Data were presented as mean ± SEM
