PHYSIOLOGICAL AND BEHAVIORAL EFFECTS OF RILUZOLE EXPOSURES IN WT AND SOD1 MUTANT ZEBRAFISH

Despite the growing use and characterization of the SOD1G93R mutant zebrafish ALS model, there is a lack of degeneration studies during chronic riluzole treatment. Most studies have focused on comparing the mutant zebrafish to control lines to show there is indeed development of ALS-like symptoms during their growth. This is the first study to treat SOD1 fish with 1 µM and 0.5 µM riluzole, chronically and for 1-week, respectively. At 10, 20, and 30 dpf, OMR, startle response, swimming activity, and body length were measured. SOD1G93R fish did not survive either of the two riluzole treatment conditions, whereas chronically riluzole-treated WT fish survived better than water- or vehicle-treated controls. SOD1G93R larvae exposed to vehicle for one week moved 0.999 mm more than chronically vehicle-treated (p = 0.015). When chronically-exposed to 1 µM riluzole, zebrafish larvae swam significantly less than water-treated (0.92 s, p = 0.019) and vehicle-treated fish (1.03 s, p = 0.012). SOD1G93R fish exposed to 1 week of 0.5 µM vehicle moved 0.98 mm/s slower than WT zebrafish in the same treatment condition (p = 0.001). Startle responses and OMR tests revealed no differences across treatments, however SOD1G93R fish responded significantly worse to clockwise stimuli than WT fish. Behavioral alterations due to strain and treatment were detectable in this study, but the spawning sensitivity of SOD1 mutants and their poor survival in riluzole presented difficulties that should be considered in future studies.