Fig. 8
Knockdown of C/EBPβ in 5XFAD mice reduces AD-like pathogenesis and rescues cognitive function. a Knockdown of C/EBPβ reduces delta-secretase and APP and Tau fragments cleaved by delta-secretase. Hippocampal tissues from both control and C/EBPβ−shRNA injected 5XFAD mice were analyzed by immunoblotting with various antibodies (n = 3 mice per group). b, c Knockdown of C/EBPβ reduces delta-secretase mRNA and enzymatic activities. Data represent mean ± s.e.m. of three mice per group (*P < 0.05, Student’s t-test). d Knockdown of C/EBPβ decreases expression levels of inflammatory cytokines. Data represent mean ± s.e.m. of three mice per group (*P < 0.05, Student’s t-test). e C/EBPβ knockdown decreases amyloid plaques and Aβ in 5XFAD mice. Quantification of number and surface area of amyloid plaques as well as measurements of Aβ levels by ELISA (right panels). Plaque analysis data represent mean ± s.e.m. of 11–17 sections from three mice in each group (*P < 0.05, **P < 0.01, Student’s t-test). Aβ ELISA represents mean ± s.e.m. of three mice per group (*P < 0.05, Student’s t-test). Scale bar, 50 μm. f Knockdown of C/EBPβ increases the spine density in the hippocampal neurons. Scale bar, 5 μm. Golgi staining was conducted on brain sections from control and C/EBPβ-shRNA injected hippocampal regions of 5XFAD mice (mean ± s.e.m.; n = 5; *P < 0.05, Student’s t-test). g Electrophysiology analysis. C/EBPβ silencing in the hippocampus rescued the LTP defects in 5XFAD 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 (5XFAD-Ct) and 3 and 4 (5XFAD-shC/EBPβ) mice. h, i Morris water maze analysis of cognitive functions. C/EBPβ deletion in the hippocampus rescues the learning and memory impairments in 5XFAD mice (mean ± s.e.m.; n = 8 mice per group; *P < 0.05, Student’s t-test)
