Zebrafish as a tool to assess developmental neurotoxicity

Abstract

The zebrafish (Danio rerio) is an emerging biological model system in toxicological studies. The zebrafish is used to fill the gap between various in vitro and mammalian models currently being used to identify mechanisms of developmental neurotoxicity. The high-throughput characteristics that contribute to the strength of this small animal model combined with novel and/or standardized high-throughput technology can be used by researchers to conduct a robust volume of developmental embryonic and larval neurotoxicity assays. Using analytical toxicological methods, dose-response-time relationships can be established for comparison to other research animal model systems and translation to humans. Toxicogenomic and targeted molecular evaluations of xenobiotics can be used to identify pathways of toxicity and linked with phenotypic and behavioral insults to define mechanisms of developmental neurotoxicity using wild-type or transgenic zebrafish. This chapter describes analytical approaches for examining toxicokinetics of xenobiotics in the developing zebrafish, imaging techniques being used to identify phenotypic neurological abnormalities, behavioral assays in embryonic and larval zebrafish, and targeted and -omic approaches to identify molecular targets and pathways of neurotoxicity for an integrated approach to investigate developmental neurotoxicity using the zebrafish model system.