Exposure to environmental concentrations of pesticides and metals can cause neurobehavioral changes that influence survival of Pacific salmon. These neurological impacts that arise from central and peripheral nervous system deficits, including inhibition of peripheral olfactory function, may block the ability to detect predators and prey, alter reproductive timing, and interfere with homing to natal streams. The fish peripheral olfactory system is highly vulnerable to the toxic effects of dissolved contaminants due to its direct contact with the aquatic environment. Olfactory injury is now documented in other aquatic species exposed to environmental pollutants, suggesting far-reaching ecological ramifications of this phenomenon. The goal of our project is to understand the mechanisms of chemical-induced olfactory injury in Pacific salmon, and based upon our findings, generate biomarkers of olfactory injury to evaluate the ecological health and remediation outcomes at Superfund sites. Our studies will also use zebrafish, a well-defined genetic model, to better understand the mechanisms of olfactory injury that are relevant to salmon. In the current application, we will continue to integrate molecular, biochemical, physiological, and behavioral endpoints using model metal olfactory toxicants that are relevant to Superfund exposures. This novel approach allows a thorough understanding of mechanisms of chemical-induced olfactory injury in fish.
In Aim 1, we will identify olfactory receptor neuron populations that are targets of cadmium (Cd) and address impaired olfactory signaling and neuron regeneration (neurogenesis) as mechanisms of Cd-mediated olfactory injury.
In Aim 2, we will investigate transcriptional and post-transcriptional control of olfaction during metal exposures. We will identify functionally-important olfactory microRNAs (miRNAs) and their gene targets that are important regulators of metal-induced olfactory injury.
In Aim 3, we will develop olfactory biomarkers generated from our work for field studies at Superfund sites. We will verify and test glutathione S-transferase (GST) isoforms as biomarkers of olfactory injury, and carboxylesterase- organophosphate protein adducts as markers of organophosphate exposures. We will use transgenic zebrafish to evaluate other common, but untested, Superfund metals as olfactory toxicants. We will incorporate our olfactory molecular biomarkers within a multiplex platform to evaluate remediation outcomes in the lower Duwamish waterway, a regional Superfund site at various stages of remediation. We have assembled a strong team of collaborators for this project whose interactions are described in the proposal. We have endeavored to be responsive to SRP objectives by using mechanistic approaches to address health hazards and remediation outcomes at Superfund sites in collaboration with EPA partners involved in Superfund site assessment.

Public Health Relevance

This project uses laboratory and field studies to address how a group of neurotoxic Superfund priority chemicals cause behavioral defects in Pacific salmon stemming from loss of olfactory function, a phenomenon linked to loss of survival in aquatic species. Our field site for these studies is a Superfund site that is home to a highly diverse group of residents, some of whom consume fish from the contaminated waterway, and thus an area of concern to a broad range of federal, state, and county agencies, including US EPA, ATSDR, NOAA fisheries, and Washington Departments of Health and Ecology. In addition to our community engagement and research activities, our project continues to develop innovative tools to help understand and mitigate the risks that hazardous waste poses to ecological and human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES004696-28
Application #
9149245
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
28
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Criswell, Susan R; Warden, Mark N; Searles Nielsen, Susan et al. (2018) Selective D2 receptor PET in manganese-exposed workers. Neurology 91:e1022-e1030
Meador, James P; Yeh, Andrew; Gallagher, Evan P (2018) Adverse metabolic effects in fish exposed to contaminants of emerging concern in the field and laboratory. Environ Pollut 236:850-861
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Heffern, Kevin; Tierney, Keith; Gallagher, Evan P (2018) Comparative effects of cadmium, zinc, arsenic and chromium on olfactory-mediated neurobehavior and gene expression in larval zebrafish (Danio rerio). Aquat Toxicol 201:83-90
Racette, Brad A; Gross, Anat; Criswell, Susan R et al. (2018) A screening tool to detect clinical manganese neurotoxicity. Neurotoxicology 64:12-18
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Rooney, James P K; Woods, Nancy F; Martin, Michael D et al. (2018) Genetic polymorphisms of GRIN2A and GRIN2B modify the neurobehavioral effects of low-level lead exposure in children. Environ Res 165:1-10
Chang, Yu-Chi; Cole, Toby B; Costa, Lucio G (2018) Prenatal and early-life diesel exhaust exposure causes autism-like behavioral changes in mice. Part Fibre Toxicol 15:18
Criswell, Susan R; Nielsen, Susan Searles; Warden, Mark et al. (2018) [18F]FDOPA positron emission tomography in manganese-exposed workers. Neurotoxicology 64:43-49
Wang, Hao; Zhang, Liang; Abel, Glen M et al. (2018) Cadmium Exposure Impairs Cognition and Olfactory Memory in Male C57BL/6 Mice. Toxicol Sci 161:87-102

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