Figure 4.

Single mild CHI-impaired long-term potentiation (LTP) and expression of synaptic proteins are prevented by knockdown of TDP-43 in APP TG mice. a~c, LTP at hippocampal CA3-CA1 synapses in WT and TG mice that received LV expressing scramble control, TDP-43-shRNA, or shRNA-resistant TDP-43. Recordings were made 30 days following single mild CHI. The data in bar graphs are means ±SEM averaged from 56 to 60 min following high-frequency stimulation (HFS). **P<0.01 compared with WT-Sham; §§P<0.01 compared with WT-TBI; ##P<0.01 compared with TG-Sham (ANOVA with Bonferroni post-hoc test, n=12~15 slices/5~6 animals/group). d, Expression of glutamate receptor subunits and PSD-95 in the hippocampus of WT and APP TG mice that received LV expressing scramble control. The analysis was performed 30 days after single mild CHI. The data are means ±SEM. *P<0.05, **P<0.01 compared with WT-LV-Scr-Sham, §P<0.05, §§P<0.01 compared with WT-LV-Scr-TBI; ##P<0.01 compared with TG-LV-Scr-Sham (ANOVA with Fisher's PLSD test post-hoc test, n=3~4 animals/group). e, Expression of glutamate receptor subunits and PSD-95 in the hippocampus of WT and APP TG mice that received LV expressing TDP-43-shRNA. The data are means ±SEM (n=3~4 animals/group). f, Expression of glutamate receptor subunits and PSD-95 in the hippocampus of WT and APP TG mice that received LV expressing shRNA-resistant TDP-43. The data are means ±SEM. *P<0.05, **P<0.01 compared with WT-LV-Resc-Sham, §P<0.05, §§P<0.01 compared with WT-LV-Resc-TBI; #P<0.05, ##P<0.01 compared with TG-LV-Resc-Sham (ANOVA with Fisher's PLSD post-hoc test, n=3~4 animals/group).