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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: Inhibition of DYRK1A proteolysis modifies its kinase specificity and rescues Alzheimer phenotype in APP/PS1 mice

Fig. 3

L41 treatment prevents DYRK1AT accumulation in astrocytes and decreases phosphorylation of STAT3α and the release of pro-inflammatory cytokines. a Representative western blot of mouse hippocampus showing higher levels of GFAP and vimentin in vehicle- (n = 6) and L41- (n = 7) treated APP/PS1 mice than in littermates (n = 6) (One-way ANOVA; GFAP: p < 0.05 and p < 0.005, respectively; vimentin: p < 0.005 and p < 0.0005, respectively). There were no statistical differences between L41- and vehicle-treated APP/PS1 mice (One-way ANOVA, ns and ns). b Laser confocal microscopy showing double staining, using anti-4G8 (white) and anti-GFAP (green) antibodies, of hippocampal slices from vehicle- (n = 6, plaques = 39) or L41- (n = 6, plaques = 38) treated APP/PS1 mice. There were no differences in GFAP (green) immunoreactivity around amyloid plaques (white) between vehicle- and L41-treated APP/PS1 mice (t-test, ns). c Representative western blot of hippocampus from mice showing higher phospho-STAT3α / STAT3α ratio in vehicle- treated APP/PS1 mice compared to littermates and L41-treated APP/PS1 mice (One-way ANOVA; pSTAT3α: p < 0.0005 and p < 0.0005, respectively; STAT3α: p < 0.05 and ns, respectively; pSTAT3α / STAT3α: p < 0.0005 and p < 0.0005, respectively) (d) ELISA quantification (MSD immunoassay) in samples from hippocampus of littermates, vehicle- and L41-treated APP/PS1 mice (n = 4, 6, and 7 mice per group, respectively). Vehicle-treated APP/PS1 mice had higher IL-1β, IL-12 (IL-12p70) and TNF-α concentrations than in littermates (One-way ANOVA: IL-1β and TNF-α, p < 0.05; IL-12p70, p < 0.005). L41-treated APP/PS1 mice had lower IL-1β, IL-12 and TNF-α concentrations than vehicle-treated APP/PS1 mice (One-way ANOVA: IL-1β, and TNF-α, p < 0.05; IL-12p70, p < 0.005). Data represent the mean ± SEM and were analyzed by one-way ANOVA followed by Tukey’s post hoc test or Student’s t-test. Significant differences between littermates and vehicle-treated APP/PS1 mice are indicated by *p < 0.05, **p < 0.005 and ***p < 0.0005. Significant differences between vehicle- and L41-treated APP/PS1 mice are indicated by #p < 0.05, ##p < 0.005 and ###p < 0.0005

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