Domoic acid disruption of neurodevelopment and behavior involves altered myelination in the spinal cord

Harmful algal blooms (HABs) produce potent neurotoxins that threaten human health. Early life exposure to low levels of the HAB toxin domoic acid (DomA) can produce long-lasting behavioral deficits, but the mechanisms involved are unknown. Using the zebrafish model, we investigated the developmental window of susceptibility to low doses of DomA and examined cellular and molecular targets. Larvae exposed to DomA (0.09 ng) at 2 days post-fertilization (dpf), but not at 1 or 4 dpf, showed deficits in startle behavior that included reduced responsiveness and altered kinematics. Similarly, myelination in the spinal cord was disorganized after exposure at 2 dpf but not 1 or 4 dpf. Time-lapse imaging revealed disruption of the initial stages of myelination. DomA down-regulated genes required for maintaining myelin structure and the axonal cytoskeleton. These results identify a developmental window of susceptibility to DomA-induced behavioral deficits involving altered gene expression and disrupted myelin structure and establish a zebrafish model for investigating the underlying mechanisms. Overall design: 12 samples were sequenced, including 2 different treatments across 2 different developmental periods. Each treatment has 3 biological replicates