Figure 5. Inhibition of eEF2K activity rescues Aβ-induced impairments in LTP. A, Western blot demonstrating that levels of phosphorylated eEF2 (Thr56), but not total eEF2, were increased in the hippocampus of APP/PS1 mice. Cumulative data are shown in the bar graph; n = 8 for wild-type (WT), n = 7 for APP/PS1. Unpaired independent t test; *p < 0.05. B, Western blot demonstrating that eEF2 phosphorylation at Thr56 was increased in postmortem human AD brain tissues compared with age-matched controls. Cumulative data are shown in the bar graph; n = 5 for both groups. Unpaired independent t test; *p < 0.05. C, Western blot experiments showing that levels of eEF2 phosphorylation were decreased in AMPKα2 KO mice. Cumulative data are shown in the bar graph; n = 6. Unpaired independent t test; *p < 0.05.D, Western blot experiments showing that levels of TSC2 phosphorylation (Ser1387) were not altered in hippocampus of APP/PS1 mice; n = 6. Unpaired independent t test; p > 0.05. E, Phosphorylation of mTOR (Ser2448) and expression of eEF1A were not affected in the hippocampus of AMPKα2 KO mice. Blots shown are representative of three independent experiments. F, Aβ caused LTP failure (gray triangles, n = 9) compared with normal LTP induction in slices treated with vehicle (open squares, n = 9). Treatment of hippocampal slices with the eEF2K inhibitor NH125 rescued Aβ-induced LTP impairment (half-filled triangles, n = 7), whereas NH125 alone did not alter LTP (gray diamonds, n = 6). G, Cumulative data showing mean fEPSP slopes 80 min after HFS based on LTP experiments in F. Unpaired independent t test; *p < 0.05. H, Representative fEPSP traces before and after HFS for LTP experiments with Aβ treatment in the presence of either NH125 or vehicle shown in F.