Neurodegenerative zebrafish models and setting up new efficacy assays

Abstract

Despite the advances in chemicals toxicity research, there is a lack of more efficient and informative toxicity approaches to evaluate the large number of existing chemicals. A major challenge is characterizing the neurotoxic potential of chemicals, which have scarce hazard data available. Thus, efforts to assess the neurotoxic potential of chemicals are needed. Our main goal is to tackle this gap and study efficient approaches to evaluate a broad spectrum of chemicals. To attain that, we propose to study several biomarkers of neurodevelopment in zebrafish model, by combining high-throughput screening technologies with different biomarkers, such as neurotransmitters and behavioral phenotyping, in order to accelerate the search for harmful/benefic chemicals and provide tools for understanding vertebrate behavior mechanisms underpinning neuroactivity. Therefore, we will develop a multidisciplinary approach, using behavior and biochemical tools, allowing the study of specific fingerprints and the establishment of a link between biochemical and behavioral alterations. Results will allow us to characterize parameters that are always affected by any chemical tested or only for a specific chemical class. The efficacy of the selected biomarkers will be assessed to screen different hazard/benefic chemicals for human and environmental health using a wild-type (WT) line and a knockout (KO) mutant line of zebrafish generated for neurodegenerative diseases. Together, those biomarkers will be used as a tool to indicate the general health status of organisms under chemical exposure, seeking relevant tools for human and environmental health. (AU)