Dantrolene inhibited impairment of dendrite intersection and synaptic density of neurons in Alzheimer’s disease cells. Neural progenitor cells were differentiated into mature cortical neurons with insulin, and dantrolene (DAN) treatment was for 3 days starting from the induction of differentiation. The mean number of intersections between dendrites and concentric circles around the cortical neurons are shown as a function of the circle distance (μm) from the soma. (A) The number of intersections was significantly less in both sporadic Alzheimer’s disease (SAD) and familial Alzheimer’s disease (FAD) cells, which was inhibited by dantrolene in sporadic Alzheimer’s disease cells. (B) The mean numbers of intersections at the distance around 150 µM from soma were less in sporadic Alzheimer’s disease (P < 0.0001) and familial Alzheimer’s disease cells (P < 0.0001) compared with controls (CON) but were significantly greater in both sporadic Alzheimer’s disease (P < 0.0001) and familial Alzheimer’s disease cells (P = 0.014) with dantrolene treatment. Interaction (F[2,12] = 42.18, P < 0.0001), cell type (F[2,12] = 273.30, P < 0.0001), and dantrolene treatment (F[1,12]= 78.48, P < 0.0001) were significant sources of variation. Statistical significance was determined by two-way analysis of variance and Sidak’s multiple comparison test. (C) Synaptic density was determined by postsynaptic marker postsynaptic density protein 95 (PSD95; red) and presynaptic marker synapsin-1 (green) double immunostaining. Scale bar, 100 μm. (D) PSD95 density was significantly less in both sporadic Alzheimer’s disease (P = 0.001) and familial Alzheimer’s disease cells (P = 0.001) compared with controls but was significantly greater in familial Alzheimer’s disease cells (P < 0.0001) with dantrolene treatment. Interaction (F[2,23] = 8 .78, P = 0.002), cell type (F[2,23] = 25.36, P < 0.0001), and dantrolene treatment (F[1,23] = 28.60, P < 0.0001) were significant sources of variation. (E) Synpapsin-1 was also significantly less in sporadic Alzheimer’s disease (P = 0.001) and familial Alzheimer’s disease P < 0.0001) cells and was significantly greater in familial Alzheimer’s disease cells treated with dantrolene (P < 0.0001). Interaction (F[2,23] = 18.12, P < 0.0001), cell type (F[2,23] = 21.46, P < 0.0001), and dantrolene treatment (F[1,23] = 7.18, P = 0.013) were significant sources of variation. The data are represented by the means ± SD from at least four independent experiments: controls and familial Alzheimer’s disease cells (N = 5) and sporadic Alzheimer’s disease cells (N = 4). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. Statistical significance was determined by two-way analysis of variance and Sidak’s multiple comparison test. DMSO, dimethyl sulfoxide.