Fig. 2: MITOL-deleted APP/PS1 mice show severe cognitive impairment, synapse alteration, and neuroinflammation.

a–c MITOL deletion exacerbated Aβ pathology-mediated cognitive decline. Indicated mice at 15 months of age were subjected to the novel object recognition test (a), Y-maze test (b), or Barnes maze test (c), respectively. Error bars indicate ±SE (a: n = 10, b: n = 10–20, c: n = 10–16). ****p < 0.0001, **p < 0.01, *p < 0.05 (one-way ANOVA, Tukey’s test). d, e MITOL deletion enhanced neuronal atrophy in the AD model mice. Brain sections of indicated mice were stained using cresyl violet (d). The lower panels show high-magnification images of the boxed regions. Arrowheads indicate neurons. The average size of each neuronal soma stained with cresyl violet was calculated from over 300 cells using ImageJ (e). Scale bar represents 50 µm. Error bars indicate ±SE (e: n = 4–6). ****p < 0.0001, ***p < 0.001, **p < 0.01 (one-way ANOVA, Tukey’s test). f, g Synapse markers, Synaptophysisn and PSD-95, were significantly reduced in the hippocampus of MITOL-deleted APP/PS1 mice at 12 months of age. Hippocampal lysates of indicated mice were immunoblotted with indicated antibodies. Error bars indicate ±SE (g: n = 4–6). *p < 0.05 (one-way ANOVA, Tukey’s test). h, i Activated microglia was increased in MITOL-deleted APP/PS1 mice. Brain sections of indicated mice at 12 months of age were immunostained with anti-IBA1 antibody (h). The lower panels show high-magnification images of the boxed regions. Scale bar represents 100 µm. The indicated mRNA in the hippocampus extracted from indicated mice at 12 months of age was evaluated by qRT-PCR. Error bars indicate ±SE (n = 4–6). **p < 0.01, *p < 0.05 (one-way ANOVA, Tukey’s test).