Fig. 6

DCA rescued the gray brain phenotype, survival, and integrated neurologic and/or muscular function in CAP-stressed fbxl4sa12470 larval zebrafish. (A?D) RC and CS enzyme activity detected in 7 dpf larvae (mean ± SEM). n = 3 each condition. (E?I) Representative images of 6 dpf age-matched fbxl4sa12470 and AB WT larvae at 6 dpf after 4 days (starting from 2 dpf) of incubation with 2.5 mM CAP alone or with DCA cotreatment. Morphological defects were obvious at 6 dpf, showing higher sensitivity of (F and H) fbxl4sa12470 larvae to 2.5 mM CAP compared with (E) AB WT larvae: gray brain phenotype (black arrows in F and bracket in H, Supplemental Figure 3), heart edema (generally not observed in WT, arrowheads in F and H), and overall body degeneration and slight bent tail (white arrow in H). (G and I) Coexposure of stressed fbxl4sa12470 larvae with 5 mM DCA improved the gray brain phenotype (clear brain in I indicated by a bracket; Supplemental Figure 3) but did not rescue the delay in swim bladder formation in either AB WT or fbxl4sa12470 larvae. Scale bar: 1 mm. (J?N) 2.5 mM CAP significantly affected development (percentage of swim bladder), survival, and neuromuscular response (percentage of tap response and touch response), and caused brain death in 7 dpf mutant larvae (Supplemental Table 2, A and B). (J and K and Supplemental Videos 6 and 7) 5 mM DCA significantly rescued the gray brain phenotype and survival and improved neuromuscular response. *P < 0.05, **P < 0.01, ***P < 0.001, Cochran-Mantel-Haenszel and ?2 test performed (Supplemental Table 2). Bar graphs are representative of the statistical analysis shown in the Supplemental Table 2, where all data details are shown.