Fig. 6

Administration of ML264 inhibits the BACE1 expression and ameliorates memory impairments in APP/PS1 mice. Five-month-old APP/PS1 mice were treated with vehicle (PBS) or ML264 (5 mg/kg, i.p, every other day) for 15 weeks. A–C WT mice (WT, n = 6), vehicle-treated APP/PS1 mice (APP/PS1 Ct, n = 6), and ML264-treated APP/PS1 mice (APP/PS1+ML264, n = 6) were trained and tested on the spatial memory version of the Morris water maze. A The escape latency time of the different groups of mice was recorded on each training day (means ± s.e.m; one-way ANOVA; *: WT versus APP/PS1 Ct, *P < 0.05, **P < 0.01, and ****P < 0.0001; #: APP/PS1 Ct versus APP/PS1+ML264, ^#P < 0.05). B Mice were given a memory retention probe trial with the escape platform removed 24 h after the last training trial. The swimming time in the target quadrant of the different groups of mice was recorded. C Time for the first crossing over the original platform site and the platform crossing time of different groups of mice. D mRNA level of BACE1 in the cerebral cortex (left) and hippocampus (right) of different groups of mice. E Representative Western blots and relative quantification of the protein expression levels of KLF5 and BACE1 in the cerebral cortex of different groups of mice. F Representative Western blots and relative quantification of the protein expression levels of KLF5 and BACE1 in the hippocampus of different groups of mice. G Immunofluorescence (×200) of the expression levels of KLF5 and BACE1 in the brain of different groups of mice. H BACE1 activity (fluorogenic BACE1 activity assay) in the brain of different groups of mice. I Levels of sAPPβ in the brain of different groups of mice. J Staining and quantification of amyloid plaques in the hippocampus among different groups of mice. K Staining and quantification of amyloid plaques in the cortex among different groups of mice. L Levels of Aβ40 and Aβ42 in the brain of different groups of mice. Data in B–F, H, I, J, K, and L are mean ± s.e.m (*P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001; one-way ANOVA)