Fig. 6: Li and VPA enhance mitochondrial OCR in patient-derived NPCs.

Analysis of oxidative phosphorylation using Seahorse Analyzer. a Oxygen consumption rate (OCR) kinetics graph showing that Li-R patient NPCs present a tendency of decreased mitochondrial OCR, which could be indicative of dysfunctional mitochondrial function as compared to CTRL cells. b Extracellular acidification rate (ECAR) kinetics graph displaying glycolysis activity for all three groups. Diagram summarizing the main OCR and ECAR results after Li (c) and VPA (d) treatments. Li treatment of Li-R NPCs lead to an increase in maximal respiration and reserve capacity. VPA treatment of Li-N NPCs lead to an increase in maximal respiration and reserve capacity. e–g OCR (e) and ECAR (f) graphs for Li treatment for 6 h. The ECAR graph shows a tendency to increase basal glycolytic activity, but no statistically significant difference was found. g Basal respiration, ATP production, maximal respiration, reserve capacity and basal glycolysis after 6 h of Li treatment. Basal respiration of Li-R cells was significantly higher after Li treatment. The means of OCR parameters and basal glycolysis from untreated CTRL, Li-N and Li-R cells were compared by one-way ANOVA. The means of OCR parameters and basal glycolysis from untreated vs. treated cells for each experimental group were compared by two-tailed unpaired t-test. h–j OCR (h) and ECAR (i) graphs after Li treatment for 1 week. j Basal respiration, ATP production, maximal respiration, reserve capacity and basal glycolysis after 1 week Li treatment. Maximal respiration and reserve capacity of Li-R cells were significantly higher after Li treatment. k–m OCR (k) and ECAR (l) graphs for VPA treatment for 1 week. m Basal respiration, ATP production, maximal respiration, reserve capacity and basal glycolysis after 1 week VPA treatment. Maximal respiration and reserve capacity of Li-N cells were significantly higher after VPA treatment. Data was analyzed by two-tailed unpaired t-test. All experiments were run in quadruplicates, and values are corrected for total protein levels. Data is presented as mean ± SEM of at least two independent experiments (n = 3 cell lines/group). NPCs neural precursor cells, CTRL control, Li-R lithium responders, Li-N lithium non-treated, ECAR extracellular acidification rate, OCR oxygen consumption rate.