Fig. 9

Preclinical candidate drug screening in dldh–/– zebrafish larvae. (A) Representative ZebraBox activity time course as in Figure 4C for WT (olive), dldh–/– (green), and dldh–/– treated with 0.5, 1.0, or 5.0 mM thiamine (black, orange, gray), respectively. Notably, at 5.0 mM thiamine, there was minimal observable swim activity (n = 3 biological replicates). (B) Four replicates of the effect of 0.1, 0.5, or 1 mM thiamine treatment from 4 dpf to 6 dpf on the swimming activity of dldh–/– zebrafish larvae. Quantitation across the dark cycles was by AUC. Four biological replicates are represented by coloring the data points red, green, blue, or purple. One-way ANOVA with multiple comparisons to dldh–/– identified treatment with either 0.1 or 0.5 mM as enhancing the swimming activity of the dldh–/– by ~100%; **P < 0.01. (C) Similarly, probucol treatment (5 μM, 4–dpf) also increased swim activity of 7 dpf dldh–/– zebrafish larvae (*P ≤ 0.05 by unpaired Student’s t test with a Bonferroni correction) but not of WT; n = 5 biological replicates per condition, n = 12 zebrafish larvae for each condition per biological replicate experiment