Zebrafish neurotoxicity models

Abstract

The field of neurotoxicology is confronted with two significant demands: the testing of an ever increasing list of chemicals, and resource limitations/ethical concerns associated with testing using traditional mammalian species. National and international government agencies have well-defined a need to reduce, refine or replace mammalian species in toxicological testing with alternative testing methods and non-mammalian models. Toxicological assays using alternative animal models may relieve some of this pressure by allowing testing of more compounds while reducing expense and using fewer mammals. Recent advances in genetic technologies and the strong conservation between human and non-mammalian genomes allow for the dissection of the molecular pathways involved in neurotoxicological responses using genetically tractable organisms such as zebrafish (Danio rerio). A constantly increasing database on basic developmental biology, gene transfers, and the rich foundation of molecular genetic and genomic data make zebrafish a powerful modeling system for revealing mechanisms in neurotoxicology. In contrast to the highly advanced knowledge base on molecular developmental genetics in zebrafish, the databases regarding pathologic lesions in zebrafish lag far behind the information available on most other domestic mammalian and avian species, particularly rodents. Therefore, to fully utilize the potential of zebrafish as an animal model for understanding neurotoxicological influences on human development and disease we must greatly advance our knowledge on zebrafish diseases and pathology.