Fig. 2.
Dantrolene ameliorated impairment of neuroprogenitor cells differentiation into immature neurons in Alzheimer’s disease cells. Differentiation of neural progenitor cells into immature neurons (differentiation day 23) was significantly impaired in both sporadic Alzheimer’s disease (SAD) and familial Alzheimer’s disease (FAD), which was inhibited by dantrolene (DAN). (A) Representative immunofluorescence images of stained immature neurons by doublecortin (DCX; red), treated with or without dantrolene for 3 days, starting on induction day 0 from induced pluripotent stem cells. Scale bar, 100 μm. (B) Differentiations of both sporadic Alzheimer’s disease cells (P = 0.004) and familial Alzheimer’s disease cells (P = 0.011) were impaired compared with controls (CON). However, the differentiations of both sporadic Alzheimer’s disease (P = 0.008) and familial Alzheimer’s disease (P = 0.008) cells were enhanced after treatment with dantrolene. Cell type and treatment were significant sources of variation (F[2,30] = 8.749, P = 0.001; and F[1,30] = 25.08, P < 0.0001, respectively) using two-way analysis of variance with Sidak’s multiple comparison tests. The data are represented by the means ± SD from six independent experiments (n = 6 for all groups). *P < 0.05; **P < 0.01. DAPI, 4′,6-diamidino-2-phenylindole; DMSO, dimethyl sulfoxide.

Dantrolene ameliorated impairment of neuroprogenitor cells differentiation into immature neurons in Alzheimer’s disease cells. Differentiation of neural progenitor cells into immature neurons (differentiation day 23) was significantly impaired in both sporadic Alzheimer’s disease (SAD) and familial Alzheimer’s disease (FAD), which was inhibited by dantrolene (DAN). (A) Representative immunofluorescence images of stained immature neurons by doublecortin (DCX; red), treated with or without dantrolene for 3 days, starting on induction day 0 from induced pluripotent stem cells. Scale bar, 100 μm. (B) Differentiations of both sporadic Alzheimer’s disease cells (P = 0.004) and familial Alzheimer’s disease cells (P = 0.011) were impaired compared with controls (CON). However, the differentiations of both sporadic Alzheimer’s disease (P = 0.008) and familial Alzheimer’s disease (P = 0.008) cells were enhanced after treatment with dantrolene. Cell type and treatment were significant sources of variation (F[2,30] = 8.749, P = 0.001; and F[1,30] = 25.08, P < 0.0001, respectively) using two-way analysis of variance with Sidak’s multiple comparison tests. The data are represented by the means ± SD from six independent experiments (n = 6 for all groups). *P < 0.05; **P < 0.01. DAPI, 4′,6-diamidino-2-phenylindole; DMSO, dimethyl sulfoxide.

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