Development of Genomics and Behavioral Assays for Understanding Neurotoxicity of Chemicals and Effects on Performance
Project ID: W912HZ-19-2-0042
Federal Agency: U.S. Army Corps of Engineers
Partner Institution: Oregon State University
Fiscal Year: 2019
Initial Funding: $69,998
Total Funding: $209,998
Principal Investigator: Tanguay, Robert
Agreement Technical Representative: Escalon, Barbara Lynn
Abstract: The goal of this project is to link chemical exposure to behavioral outcomes that are suitable for modeling hazard assessment. Exposure to xenobiotic chemicals can exert neurotoxicity. There is an increasing pressure to reduce the use of animals in toxicity testing. To accomplish this, predictive toxicity models are needed. The embryonic zebrafish develops rapidly, its genome is 80% similar to humans, and a high number of human disease states are recapitulated in the zebrafish. These qualities make it an ideal model for the detection of chemical bioactivity and translation of the bioactivity to higher vertebrates. The proposed project also seeks to understand the impact of chemical exposures on the gut microbiome. The data will be used to build predictive models of chemical hazard potential that are translatable to higher vertebrates.
b. Specific Aims
Specific Aim 1 – Measure multiple dimensions of neurotoxicant impacts in the developmental zebrafish.
Specific Aim 2 – Evaluate the gross morphological, behavioral and gut microbiome effects of acute exposure to neurotoxicants in adult zebrafish.
c. Methodology
We will expose developing zebrafish to a broad 7 concentration curve to identify adverse morphological effects associated with 4 chemicals:
permethrin, chlorpyrifos oxon, PFOS, the rest to be determined in consultation with ERDC. In addition to morphological changes, behavioral effects will be assessed at both the embryonic and larval stages. The concentrations from the developmental zebrafish study will be used to inform the subsequent adult study.
The same chemicals will be tested in acute exposure to adult zebrafish for 21 days. The study will use 6 concentrations with a sufficient population for robust statistics. Each exposed adult zebrafish will be assessed for exercise fitness, social behavior and cognition using custom-designed and constructed behavioral assessment tools already in place in the Tanguay Lab. At the end of the experiment, the adult fish will be evaluated for gross morphology changes such as weight and length differences from the control fish. Tissue samples will be collected for analysis of transcriptome changes in the brain, intestinal microbiome differences and the future option of chemical body burden.