Figure 5
From: Amyloid-β induces NLRP1-dependent neuronal pyroptosis in models of Alzheimer’s disease
Caspase-1 silencing ameliorated neuronal pyroptosis and cognitive deficits in APPswe/PS1dE9 mice. Data from 6.5-month-old APP/PS1 and wild-type (WT) mice after 6 weeks of treatment with caspase-1 siRNA or control siRNA using a miniosmotic pump. The results of behavioral tests were assessed during last 6 days of siRNA treatment period. (a) Escape latency of each group in the hidden-platform training of Morris water maze. Data were analyzed by two-way repeated-measures ANOVA. #P<0.05 versus WT mice treated with control siRNA. §P<0.05 versus APP/PS1 mice treated with control siRNA. (b) Data from probe trials are presented as percentage of time spent in the target quadrant (Q1) versus the averaged time spent in all other (a.o.) quadrants. Data were analyzed by independent sample t-test. *P<0.05 versus averaged time spent in a.o. quadrants. After behavioral testing, the caspase-1 siRNA or control siRNA-treated APP/PS1 mice were killed for the following biochemical assays. (c) Neuronal pyroptosis was detected using the TUNEL staining assay in the cerebral cortex and hippocampus of siRNA-treated APP/PS1 mice. Neurons with deep black nuclei were identified as TUNEL-positive neurons. Scale bars: 20 μm. (d) Quantitative analysis of the percentage of TUNEL-positive cells among the experimental groups. *P<0.05 versus control siRNA-treated group. (e) Western blot analysis of cleaved IL-1β (p17) in brain tissues and densitometrical quantification. β-Actin was used as a loading control. *P<0.05 versus control siRNA-treated group. All data are shown as mean±S.E.M. For behavioral testing, n=18 male mice per group. For biochemical analyses, n=6 male mice per group
