Figure 5.

Overexpression of STAT1KR ameliorates hTau-induced memory deficits. AAV-hTau-eGFP (1.5×10¹³ vg/mL) with AAV- K410/K413R-STAT1 (STAT1KR), (1.0×10¹³ vg/mL) or not were stereotaxically injected into the hippocampal CA3 of 2-mon-old C57 mice. The learning and memory ability were detected 1 month later. (A, B) Upregulation of STAT1KR was confirmed by Western blotting and immunohistochemical staining. (C) The representative swimming paths of each group during the test phase. (D) Upregulation of STAT1KR ameliorated hTau-induced spatial learning deficits shown by the decreased escape latency during 6 consecutive days training in Morris water maze (MWM) test (n = 10 each group). *, p < 0.05, **, p < 0.01, hTau vs Vec; #, p < 0.05 hTau vs hTau+STAT1KR. (E-H) Upregulation of STAT1KR ameliorated hTau-induced spatial memory deficits shown by the decreased latency to reach the platform quadrant (E), and the increased crossing time in the platform site (F) measured at day 7 by removed the platform in MWM test; while the time spent in the target quadrant had no change, and no motor dysfunction was seen (H) (n = 10 each group). (I) Upregulation of STAT1KR ameliorated hTau-induced cognition impairment shown by increased time spending in exploring the new novel object measured at 24 h during New Novel object recognition test (n = 9 each group). (J, K) Upregulation of STAT1KR ameliorated hTau-induced contextual memory deficits measured at 24 h during contextual fear conditioning test (n = 10 each group). After the mice received training by subjecting to 3 min unsignaled foot-shocks, the percent of freezing time was represented (J). At 24 h after the training, the animals were put back into the conditioning chamber for 3 min (no electrical stimulation), the percent of total freezing time which represented memory ability was represented (K). Data were presented as mean ± SEM. *, p < 0.05, **, p < 0.01, ***, p < 0.001.