Fig. 6.
Dantrolene significantly inhibited N-methyl-d-aspartate (NMDA) mediated elevation of cytosolic Ca2+ concentrations ([Ca2+]c) in induced pluripotent stem cells from Alzheimer’s disease patients. NMDA (500 µM) induced greater overall exposure of the integrated cytosolic Ca2+ represented by the area under curve (AUC; A–D) in sporadic (SAD) and familial (FAD) Alzheimer disease cells (P = 0.041 for sporadic Alzheimer’s disease, P = 0.008 for familial Alzheimer’s disease respectively) compared with normal human subjects (CON). Dantrolene (DAN, 30 µM) ameliorated the NMDA-mediated elevation of [Ca2+]c and AUC in familial Alzheimer’s disease cells (P = 0.436 for peak, P < 0.0001 for AUC, respectively; B and D). All data are expressed as medians [25th, 75th] from three independent experiments (N = 3). The data in C were nonparametric and analyzed by the Kruskall–Wallis test (P = 0.020) followed by Dunn’s multiple comparison tests. The data for D were also nonparametric and analyzed using the Kruskal–Wallis test (P < 0.001) followed by Dunn’s multiple comparison tests. *P = 0.041, **P = 0.008, ****P < 0.0001.

Dantrolene significantly inhibited N-methyl-d-aspartate (NMDA) mediated elevation of cytosolic Ca2+ concentrations ([Ca2+]c) in induced pluripotent stem cells from Alzheimer’s disease patients. NMDA (500 µM) induced greater overall exposure of the integrated cytosolic Ca2+ represented by the area under curve (AUC; A–D) in sporadic (SAD) and familial (FAD) Alzheimer disease cells (P = 0.041 for sporadic Alzheimer’s disease, P = 0.008 for familial Alzheimer’s disease respectively) compared with normal human subjects (CON). Dantrolene (DAN, 30 µM) ameliorated the NMDA-mediated elevation of [Ca2+]c and AUC in familial Alzheimer’s disease cells (P = 0.436 for peak, P < 0.0001 for AUC, respectively; B and D). All data are expressed as medians [25th, 75th] from three independent experiments (N = 3). The data in C were nonparametric and analyzed by the Kruskall–Wallis test (P = 0.020) followed by Dunn’s multiple comparison tests. The data for D were also nonparametric and analyzed using the Kruskal–Wallis test (P < 0.001) followed by Dunn’s multiple comparison tests. *P = 0.041, **P = 0.008, ****P < 0.0001.

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