Fig. 6.

Activation of SIRT3 by honokiol prevents MAM formation and exerts neuroprotective effect in diabetic mice. a, b Western blot analysis of SIRT3 expression in the hippocampus from diabetic mice with or without honokiol (HKL) treatment. Diabetic mice received intraperitoneal injections of HKL (40 mg/kg/day) for 8 weeks. β-actin served as the loading control. N = 6 mice/group. (c-e) Western blot analysis of IP3R, GRP75, and VDAC1 expression in VDAC1 immunoprecipitate from hippocampal tissue. N = 3 mice/group. f Representative electron micrograph images of ER-mitochondria contacts in the hippocampus of diabetic mice with and without honokiol (HKL). Scale bar = 100 nm. g, h Quantitative analysis of the distance between the mitochondria and ER (g) and the length of contacts (h). N ≥ 100 contacts from 4 mice per group. i, j Western blot analysis of Synaptophysin (SYP) and postsynaptic density protein 95 (PSD95) expression in the hippocampus. β-actin was used as the loading control. N = 3 mice/group. (k, l) Preference index during training and testing phase in novel object recognition (NOR) test. N = 9 mice/group. m-r Spatial learning and memory as measured by the Morris water maze (MWM) test. Latency to find the hidden platform during 5 consecutive training days (m). Representative swimming paths of each group during the test phase (n). Escape latency to reach the absent platform (o), platform crossing times (p), duration in the target quadrant (q), and average swimming speed (r) during the probe test on the 7th day. N = 9 mice/group. Data were expressed as mean ± SD for (a–e, i, j), mean ± SEM for (h, k–r), and median and range (25th–75th percentile) for (f, g), *p < 0.05, **p < 0.01, ***p < 0.001