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Metabolomic analysis and nicotinamide riboside treatment of tbk1 mutant zebrafish. A Metabolite set enrichment analysis showing the enrichment ratio and statistical significance of metabolic pathways in 6 dpf tbk1 mutant zebrafish compared to their noninjected controls (over representation analysis using Metaboanalyst 6.0 with significantly affected metabolites, p < 0.01). B Mass spectrometry quantification of NAD + , quinolinic acid and nicotinamide in tbk1 mutant or NI zebrafish (unpaired t test, p = 0.002, p < 0.001 and p < 0.001, respectively). C Schematic representation of the Nicotinamide riboside (NR) and NAD+ salvage pathway affected in tbk1 mutant zebrafish (NRK, nicotinate riboside kinase; NMNAT, nicotinamide mononucleotide adenylyltransferase). D Schematic timeline used for the treatment of tbk1 CRISPR-Cas9-injected or NI zebrafish with 10 µM NR or 0.1% DMSO in zebrafish embryo water. E Quantitative analysis of larval free-swimming motor behavior upon incubation with NR (one-way ANOVA with Tukey’s multiple comparisons test). *p < 0.05, ***p < 0.001). F Survival rate of tbk1 mutant or NI larvae upon incubation with NR.
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