Fig. 3

Effects of aldose inhibition are corroborated in vivo in pmm2 mutant zebrafish (A) Schematic representation of imaging and treatment of zebrafish. Briefly, 5-dpf wild-type and pmm2 embryos were placed one per well in a 12-well culture dish and treated daily with either 20 ?M epalrestat or vehicle, refreshing the media daily. After 15 min of sensory deprivation, locomotor activity is monitored for 10-min intervals each day (6?10 dpf) using the Zebrabox system. (B) Track of swim paths of wild-type and pmm2 zebrafish with and without epalrestat treatment on 6 and 8 dpf. Slow speed is indicated in green, while fast speed is indicated in red. (C) Epalrestat increases swimming distance (mm). Epalrestat significantly increased swimming distance at 6 and 7 dpf in pmm2 mutant zebrafish. (D) Epalrestat increases number of initiated swim events. Epalrestat significantly increased the number of initiated swim events. Mixed-effect analysis with repeated measures was used to statistically evaluate data. Means are represented with SD. e, p value reflecting the effect of epalrestat treatment; lt, p value reflecting the length of treatment; g, p value reflecting the effect of genotype calculated by statistical analysis. The number of biological (n) and technical (t) replicates was wild-type, n = 42?46, t = 1; pmm2, n = 22?51, t = 1.