Figure 6.

Silencing of TDP-43 prevents single mild CHI-accelerated cognitive decline in APP TG mice. a, Memory retention was assessed using the novel object recognition (NOR) test in WT and APP TG mice that received LV expressing scramble control. The test was conducted 30 days after single mild CHI. The data are means ±SEM. **P<0.01 compared with WT-LV-Scr-Sham, §§P<0.01 compared with WT-LV-Scr-TBI; ##P<0.01 compared with TG-LV-Scr-Sham (ANOVA with Bonferroni post-hoc test, n=8~11 animals/group). b, Spatial learning and memory retention were assessed using the Morris water maze (MWM) test. The data are means ±SEM (ANOVA with repeated measures). The probe test was conducted 24 hrs following 7 days of learning acquisition training. The data are means ±SEM. **P<0.01, compared with WT-LV-Scr-Sham; §P<0.05 compared with WT-LV-Scr-TBI; #P<0.05 compared with TG-LV-Scr-Sham. The data are means ±SEM. ***P<0.01 (ANOVA with Bonferroni post-hoc test). c, NOR test in WT and APP TG mice that received LV expressing TDP-43-shRNA. The data are means ±SEM (n=10 animals/group). d, MWM test in WT and APP TG mice that received LV expressing TDP-43-shRNA. e, NOR test in WT and APP TG mice that received LV expressing shRNA-resistant TDP-43. The data are means ±SEM. **P<0.01 compared with WT-LV-Resc-Sham, §§P<0.01 compared with WT-LV-Resc-TBI; ##P<0.01 compared with TG-LV-Resc-Sham (ANOVA with Bonferroni post-hoc test, n=8~10 animals/group). f, MWM test in WT and APP TG mice that received LV expressing shRNA-resistant TDP-43. The data are means ±SEM. ***P<0.01 (ANOVA with repeated measures). The probe test was conducted 24 hours after 7-day learning acquisition training. **P<0.01 compared with WT-LV-Resc-Sham, §§P<0.01 compared with WT-LV-Resc-TBI; #P<0.05 compared with TG-LV-Resc-Sham (ANOVA with Bonferroni post-hoc test).