Fig. 6: Mitophagy stimulation forestalls memory loss and ameliorates both Aβ and Tau pathologies in 3xTg AD mice.
The 3xTg AD mice were treated with Kaem or Rhap (100 mg kg−1 d−1) via oral gavage for 2 months starting from 12.5 months of age. a, Representative images of the swimming tracks of mice at day 7 in the Morris water maze test (n = 6 mice per group). b, Latency to the platform of mice from days 1 to 6. c, Platform frequency of mice in the probe trial at day 7. d,e, Effects of Kaem and Rhap on spontaneous alternation (d) (Y maze) and novel object recognition/NOR (e). f,g, Soluble and insoluble Aβ1–40 and Aβ1–42 levels in hippocampal tissues. n = 5 mice in all groups. h, Immunohistochemical analysis of Aβ load in 3xTg AD mice hippocampi and cortices under Kaem or Rhap treatment. Experiments were repeated twice independently, with similar results. i, Quantification of Aβ load per ROI in images from h. n = 10 random areas in the ROIs from 3 mice per group. j–l, Semi-quantification of western blot data showing effects of Kaem and Rhap on the levels of full-length APP (FL-APP), CTF-β and CTF-α in hippocampal tissues from the 3xTg AD mice (n = 3 biologically independent samples). m, Representative immunofluorescence staining of AT8-positive cells in the cortex and hippocampus of 3xTg AD mouse brains. Experiments were repeated twice independently, with similar results. The blue and red squares denote designated brain regions were magnified. n, Quantified data of m (n = 10 random areas in the ROIs from 3 mice in each group). o, Effects of Kaem and Rhap on the expression levels of different p-Tau sites (Thr181, Ser202/Thr205, Thr217 and Thr231) in hippocampal tissues from the 3xTg AD mice (n = 3 mice per group). All quantitative data are shown as mean ± s.e.m. Two-way ANOVA followed by Tukey’s multiple comparisons test (b–g, i–l, n). NS, no significance; *P < 0.05, **P < 0.01, ***P < 0.001. Additional data on the mechanisms of mitophagy induction by Kaem and Rhap in mice are shown in Extended Data Fig. 4. Original western blot gels for o are included in Source Data Fig. 3.
