Fig. 7
Reduction of C/EBPβ gene dose reverses AD-like pathologies and alleviates cognitive impairments in old 3xTg mice. a Reduction of C/EBPβ decreases delta-secretase and APP and Tau cleavage by delta-secretase. The hippocampal tissues were analyzed by immunoblotting (n = 2 mice per group). b, c Reduction of C/EBPβ reduces delta-secretase mRNA and enzymatic activities. Data represent mean ± s.e.m. of three mice per group (*P < 0.05, one-way ANOVA). d Reduction of C/EBPβ decreases expression levels of inflammatory cytokines. Data represent mean ± s.e.m. of three mice per group (*P < 0.05, **P < 0.01, one-way ANOVA). e Amyloid plaques are decreased in 3xTg/C/EBPβ +/− mice. Thioflavin S staining showing the Aβ plaques in the frontal cortex (left panels). Scale bar, 50 μm. Plaque analysis data represent mean ± s.e.m. of 12–19 sections from three mice in each group (right, *P < 0.05, Student’s t-test). Aβ ELISA represent mean ± s.e.m. of three mice per group (lower, *P < 0.05, Student’s t-test). f Tau pathologies are reduced in 3xTg/C/EBPβ +/− mice. The brain sections of 3xTg and 3xTg/C/EBPβ +/− mice (10 months old) were immunostained with AT8 (upper left panels) and AT100 antibody (lower left panels) (mean ± s.e.m.; 12–18 sections from three mice, *P < 0.05, Student’s t-test). Scale bar, 50 μm. g Spine density in the hippocampus determined by Golgi staining (mean ± s.e.m.; n = 4; *P < 0.05, Student’s t-test). Scale bar, 5 μm. h Electrophysiology analysis. C/EBPβ reduction in the hippocampus rescued the LTP defects in aged 3xTg mice (mean ± s.e.m.; n = 6 in each group; *P < 0.05, Student’s t-test). Shown traces are representative fEPSPs of four samples recorded at the time points 1 and 2 (3xTg/C/EBPβ +/+) and 3 and 4 (3xTg/C/EBPβ +/−). i, j Morris water maze analysis of cognitive functions. C/EBPβ reduction in the hippocampus rescues the learning and memory impairments in 3xTg mice (mean ± s.e.m.; n = 8 mice per group; *P < 0.05, Student’s t-test)
