Fig. 6

HDAC6 inhibitor rescues oxidative stress and mitochondrial transport by elevating Prx1 acetylation in 5xFAD mice. TBA (100 mg/kg) was i.p. injected to 6-month-old 5xFAD female mice for 4 weeks. Five mice were used in each group. Cryosectioned brain slice were used in (a, c and d). Brain lysates were used in (b). a Reduced acetylation of Prx1 is recovered by TBA in 5xFAD mice. Representative images of Ac-Prx1 immunoreactivity in CA1 are shown in left panel and quantitative graph are in right panel. b, c Oxidative stress is recovered by TBA in 5xFAD mice. Representative immunoblot (left) and quantitative analysis (right) of 4-HNE are shown in b. Representative DAB stained images (left) against indicated antibodies and quantitative analysis (right) are shown in c. Immunoreactivity of 4-HNE and 8-OHdG was quantified in cortex and CA1, respectively. d Mitochondrial transport is rescued by TBA in 5xFAD mice. Anti-Tom20 shows mitochondrial distribution in CA1. Representative images are shown in left panel. Tom20 immunoreactivity in right panel was quantified as the ratio of intensity in soma to that in stratum radiatum. Data are presented as mean ± SEM (n = 5 per group). *P < 0.05, **P < 0.01, ***P < 0.001 (two-way ANOVA, Bonferroni post-hoc test), LT: wild-type littermate, 5x: 5xFAD, V: vehicle, TBA: Tubastatin A, scale bar: 10 μm