Impacts of developmental exposures to the harmful algal bloom toxin, domoic acid, on neural development and behavior
Jennifer Panlilio, Ph.D., 2019
Mark Hahn, Co-advisor
Neel Aluru, Co-advisor
Domoic acid (DomA) is a harmful algal bloom toxin that accumulates in seafood and affects human health. Developmental exposure leads to long-term changes in behavior, neural connectivity, and brain morphology. To determine the underlying mechanisms of toxicity, this dissertation sought to: i) Establish the developmental susceptibility window for DomA toxicity, ii) Characterize the behavioral consequences of exposures, and iii) Identify the cellular targets and processes perturbed by DomA. First, I found that exposure at 2 days post fertilization led to altered startle responses, myelination defects, and the downregulation of axonal and myelin structural genes. In DomA-treated larvae, I found that Mauthner cells — hindbrain neurons required for short-latency startles — were lost in a majority of larvae, and that oligodendrocytes had shorter myelin sheaths and may be aberrantly myelinating neuronal cell bodies. Mauthner axon loss may lead to an environment where oligodendrocytes myelinate neuronal cell bodies in the absence of adequate targets. Indeed, pharmacological treatment that reduced the oligodendrocyte number also reduced the number of myelinated neuronal cell bodies. Together, these results indicate that DomA exposure targets specific cells, disrupts myelination, and leads to behavioral deficits. These mechanistic insights support hazard assessments of DomA exposures in humans during critical periods in development.