Fig. 6: UMI-77 ameliorates cognitive decline and amyloid pathologies in the APP/PS1 mouse model of Alzheimer’s disease. | Nature Communications

Fig. 6: UMI-77 ameliorates cognitive decline and amyloid pathologies in the APP/PS1 mouse model of Alzheimer’s disease.

From: Pharmacological targeting of MCL-1 promotes mitophagy and improves disease pathologies in an Alzheimer’s disease mouse model

Fig. 6

a mt-Keima signal induction by UMI-77 in the mt-Keima mouse brain hippocampus samples. Mice were injected with 10 mg/kg UMI-77 for 6 h and samples were analyzed by fluorescence microscopy (**p < 0.01 (P = 0.0083), two-tailed t test). Scale bar, 100 µm. b The number of times a mouse crossed the platform within 60 s after removing the platform by training with four days ((WT, n = 5), (APP/PS1 + Veh, n = 7), (APP/PS1 + UMI-77, n = 5), **p < 0.01 (P = 0.0053), two-tailed t test). c Latency to escape to a hidden platform in the Morris water maze during a 4-day training period ((WT, n = 5), (APP/PS1 + Veh, n = 7), (APP/PS1 + UMI-77, n = 5), *p < 0.05 (P = 0.0334), two-tailed t test). d Mice were treated as in b and brain tissues were analyzed for soluble and insoluble Aβ1–42 levels, using ELISA (mean ± S.E.M.; *p < 0.05 (P = 0.0463), two-tailed t test). Box plots indicate median (middle line), 25th, 75th percentile (box) and minima and maxima (whiskers). e Mice were treated as in b and IHC of whole brains was performed to stain for amyloid-beta (Aβ) plaques (6E10 antibody, green), astrocytes (GFAP antibody, red) and nuclei (DAPI, blue). Scale bar, 1000 μm; insets: Scale bar, 100 μm. f Mice were treated as in b and the levels of the indicated cytokine levels were measured by ELISA using whole brain lysates (mean ± S.E.M.; *p < 0.05, ns, not significant, two-tailed t test). Box plots indicate median (middle line), 25th, 75th percentile (box) and minima and maxima (whiskers). g Electron microscopy images of mice brain hippocampal tissues. Insets (blue boxes) show mitochondria. Scale bars, 5 µm; insets: Scale bars, 2 µm. Source data are provided as a Source Data file.

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