Figure 3.

Knockdown of TDP-43 reduces repeated mild CHI-induced neuroinflammation and neuropathology in WT animals. a, Schematic illustration of the experimental protocol. WT mice at two months of age were stereotaxically injected with LV 30 days prior to three repeated mild CHI (once a day for three days) and all the assessments were performed 30 days after mild CHI. b, Immunostaining analysis of immunoreactivity of GFAP in the ipsilateral hippocampus of WT mice that received LV expressing Scramble control, TDP-43-shRNA, or shRNA-resistant TDP-43. The data are means ±SEM. **P<0.01, ***P<0.001 compared with LV-Scr-Sham; §§P<0.01, §§§P<0.001 compared with LV-Scr-TBI; ###P<0.001 compared with LV-shRNA-TBI (ANOVA with Bonferroni post-hoc test, n=5 animals/group). Scale bars: 200 and 40 μm. c, Immunoreactivity of Iba1 in the ipsilateral hippocampus of WT and APP TG mice that received LV expressing scramble control, TDP-43-shRNA, or shRNA-resistant TDP-43. The data are means ±SEM. **P<0.01, ***P<0.001 compared with LV-Scr-Sham; §§P<0.01, §§§P<0.001 compared with LV-Scr-TBI; ###P<0.001 compared with LV-shRNA-TBI (ANOVA with Bonferroni post-hoc test, n=5 animals/group). Scale bars: 200 and 40 μm. d, Immunoblot analysis of BACE1 and p-tau181 in the ipsilateral hippocampus in WT animals that received LV-Scramble, -TDP-43-shRNA or -Rescue. The data are means ±SEM. **P<0.01, ***P<0.001 compared with sham (ANOVA with Fisher's PLSD post-hoc test, n=6).