Fig. 3: Altered basal glycolysis and spare respiratory capacity in SETD1A deficient neurons. | Schizophrenia

Fig. 3: Altered basal glycolysis and spare respiratory capacity in SETD1A deficient neurons.

From: Metabolic contributions to neuronal deficits caused by genomic disruption of schizophrenia risk gene SETD1A

Fig. 3

A Relative expression of glycolytic enzymes in D30 cortical spheroids (n = 3 wells per line, from 3 independent differentiations). B Lactate levels in media obtained from D34 neuronal cultures (n = 10 wells per line from 2 independent differentiations). C Diagram showing glycolysis pathway and mitochondrial respiratory complex, highlighting the effects of small molecule inhibitors used in Seahorse assays to measure glycolytic and mitochondrial stress. D Results of glycolytic stress assay in WT and SETD1A+/− neurons at D34. (left) Seahorse curves showing basal glycolysis and responses to 10 mM glucose, 2 μM oligomycin and 50 mM 2-DG over time (mins). Extracellular acidification rate (ECAR) was normalised to nuclei number post assay. (right) Quantification of glycolytic function from the same experiments (error bars = sem, n = 55 well (WT), 52 wells (SETD1A+/− Clone 1), 53 wells (SETD1A+/− Clone 2) from 3 independent differentiations). E Results of mitochondrial stress assay in WT and SETD1A+/− neurons at D34. (left) Seahorse curves showing basal respiration and responses to 2 μM oligomycin, 1 μM FCCP, and 0.5 μM rotenone/antimycin-A over time (mins). Oxygen consumption rate (OCR) was normalised to nuclei number post assay. (right) Quantification of respiratory function from the same experiments (error bars = sem, n = 32 wells (WT), 27 wells (SETD1A+/− Clone 1), 33 wells (SETD1A+/− Clone 2) from 3 independent differentiations). Data represented are mean ± sd unless otherwise indicated. For all comparisons, one-way ANOVA with Dunnett’s multiple comparisons test was performed *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.

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