Fig. 3: Trametinib induces adult cortical neurogenesis in the 5XFAD mouse brain. | Experimental & Molecular Medicine

Fig. 3: Trametinib induces adult cortical neurogenesis in the 5XFAD mouse brain.

From: Trametinib activates endogenous neurogenesis and recovers neuropathology in a model of Alzheimer’s disease

Fig. 3

a Scheme of trametinib administration to 5XFAD mice for (b) and (c). Trametinib was administered to 5-month-old 5XFAD mice for 2.5 months. b, c Immunofluorescence staining images (b) and quantification (c) of Neurod1+ Sox2+ Gfap+ triple-positive cells in the cortex of 7.5-month-old 5XFAD mice. Arrows indicate triple-positive cells. b The lower panel represents triple-positive cells in a high-magnification image. n = 3 mice per group; sagittal sections from each mouse. Scale bars, 20 or 100 μm. Normalized to the 5XFAD-vehicle group. d Scheme of trametinib administration to 5XFAD mice for (e) and (f). Trametinib was administered to 7-month-old 5XFAD mice for 1.5 months. e, f Images for EdU incorporation analysis (e) and changes in EdU-positive cell numbers (f) in the cortex of 8.5-month-old 5XFAD mice. Arrows indicate stained cells. n = 3 mice per group, n = 2 ~ 3 serial sagittal sections from each mouse. Scale bars, 100 μm. Normalized to the 5XFAD-vehicle group. g, h Immunofluorescence staining images (g) and quantification of EdU+NeuN+ cell numbers (h) in the cortex of 8.5-month-old 5XFAD mice. Arrows indicate stained cells. The lower panel represents EdU+ NeuN+ double-positive cells at high magnification. n = 3 mice per group, n = 2 ~ 3 serial sagittal sections from each mouse. Scale bars, 20 or 100 μm. Normalized to the 5XFAD-Trametinib group. i Scheme of trametinib administration to 5XFAD mice for (j–m). Trametinib was administered to 9-month-old 5XFAD mice for 1.5 months. j, k Dcx level in the lysate of the cortex of 11-month-old 5XFAD mice (j) and quantification of band intensity (k). l, m Immunohistostaining (l) and counting (m) of NeuN+ EdU+ double-positive cells in the cortex of 11-month-old 5XFAD mice. Arrows indicate stained cells. n = 3 mice per group; sagittal sections from each mouse. Scale bars, 50 μm. Data are representative of three independent experiments, and values are expressed as the mean ± SEM. P values were obtained by Student’s t-test. *p < 0.05 and **p < 0.005.

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