Fig. 5.

MST1 Knockdown alleviates cognitive impairment and mitochondrial damage in 8-month 5xFAD mice. A Schematic of experimental proposition in vivo. AAV-GFP-vehicle and AAV-GFP-shMST1 were injected into the hippocampus of 7-month-old C57 mice and 5xFAD mice, and then the mice were divided into four groups: C57 + AAV-vehicle, C57 + AAV-shMST1, 5xFAD + AAV-vehicle, and 5xFAD + AAV-shMST1 for experiments. One month later, MWM test was performed, and finally all mice were euthanized for other experiments. B Western blotting was used to analyze the levels of hippocampus MST1 and p-MST1 after AAVs injection. C Quantitative analysis of MST1 and p-MST1 in hippocampus (n = 3). D MST1 mRNA levels in the hippocampus after AAVs injection were detected using RT-qPCR (n = 3). E–I MWM test results of four groups of mice, including swimming speed (E), escape latency (F), total time spent in the target quadrant (G), number of platform crossings (H), representative traces on fifth day the MWM training period (I). (n = 12/group). J-K Representative immunoblotting bands (J) and relative expression (K) of mitochondrial dynamics (OPA1, MFN2, Drp1, Fis1) and mitochondrial biogenesis (PGC1α, Nrf1) related proteins in hippocampus after AAVs injection. L Representative images of mitochondrial ROS in the hippocampal DG region measured by MitoSOX Red staining (Scale bar is 20 µm). Nuclei were stained in blue (DAPI). M Quantitative analysis of MitoSOX Red staining (n = 4). All data represent means ± SEMs. *, Comparison between C57 + AAV-vehicle and 5xFAD + AAV-vehicle group, *p < 0.05, **p < 0.01, ***p < 0.001. #, Comparison between 5xFAD + AAV-vehicle and 5xFAD + AAV-shMST1 group, #p < 0.05; ##p < 0.01, ###p < 0.001