Figure 4: In vivo efficacy of 1 against amyloid pathology and cognitive defects. | Nature Communications

Figure 4: In vivo efficacy of 1 against amyloid pathology and cognitive defects.

From: Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer’s disease

Figure 4

(a) Determination of Aβ levels (i,ii) and loads of 4G8-immunoreactive (iii, top, brown) and Congo red-positive (iii, bottom, red) amyloid plaques in the brains of 5 × FAD mice after 30-day treatment with 1. ELISA analyses were performed in triplicate per sample to quantify Aβ oligomers or aggregates as well as SDS-soluble, FA-soluble, and total Aβ40 and Aβ42 (ii) (n=7 and 10 for vehicle- and 1-treated 5 × FAD mice, respectively). Aβ-immunohistochemistry (brown) or Congo red staining (red, inset) was conducted in the brains of vehicle- or 1-treated 5 × FAD mice (iii). The area of 4G8-immunoreactive amyloid deposits or the total number of congophilic amyloid plaques in the same cortical region of interest was measured in five brain sections taken from each animal. Representative microscopic images of cortical or subiculum area in the Congo red-stained (red) brain sections of 5 × FAD mice. ctx, cortex; hip, hippocampus, cc; corpus callosum, sub; subiculum. Scale bars=100 μm. All bars denote mean±s.e.m. (n=14 and 17 for vehicle- and 1-treated 5 × FAD mice, respectively). *P<0.05, **P<0.01, or ***P<0.001 by unpaired two-tail t-test. (b) Enhancement of cognitive performance by 1 in the 5 × FAD mice. Using the Morris water maze (MWM) test, spatial learning and memory performance was compared between 5 × FAD and their littermate wild-type mice after 30-day treatment with vehicle or 1. (i) The escape latency time was measured every day for 5 days from the day of the 30th drug treatment. (iiiv) The probe trials were conducted at 3 h after the final trial of the MWM test. ii, The images depict the representative traces of mice to search for the escape platform in the water maze for 60 s. (iii,iv) Bars denote the time when they reached the platform area (iii) and stay in the target quadrant (NW, grey area in ii; iv). The statistical comparisons were performed between 5 × FAD and their wild-type littermate mice with vehicle (#), or between vehicle and 1 treatment in 5 × FAD mice (*). All values denote mean±s.e.m. (n=14 and 17 for vehicle- and 1-treated 5 × FAD mice, respectively; n=17 for vehicle-treated wild-type mice). *P<0.05, **,##P<0.01 or ***,###P<0.01.

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