Fig. 5: Restored mitochondrial respiration and synaptic function by supplementation with NMN or PG in ABCA7^−/− iPSC-derived neurons.

A, B, E, F Mitochondrial respiration in neurons derived from isogenic control and ABCA7^−/− iPSCs (#1) was measured by Mito Stress Test Kit through Seahorse XFe96 Extracellular Flux Analyzer with PG_18:2-18:2 (A, B; 50 µM) or NMN (E, F; 100 µM) administration for 1 day 7 weeks after differentiation from NPCs. DMSO or DDW was used as a control, respectively. The OCR measurements were normalized with cell density determined by nuclear DNA staining with DAPI (n = 5–7 technical replicates/group). A.U., arbitrary unit. C, G Frequency of spontaneous firing was measured in the control and ABCA7^−/−neurons (#1) before and after administration with PG_18:2-18:2 (C; 50 µM), NMN (G; 100 µM), or respective controls (n = 7–8 technical replicates/group). Data were normalized to those before adding the compound. D, H The ABCA7^−/−neurons (#1) were treated with PG_18:2-18:2 (D; 50 µM), NMN (H; 100 µM), or respective controls 1 week after the differentiation into neurons for 7 weeks and number of burst firings represents were monitored (n = 4–5 technical replicates/group). Data represents mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 by paired t-tests (C, G), Tukey–Kramer post hoc analysis of Two-way ANOVA (B, F) or repeated measures two-way ANOVA (D, H).