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University of Washington

Superfund Research Program

Mechanisms and Biomarkers of Metal Olfactory Injury in Salmon

Project Leader: Evan P. Gallagher
Co-Investigators: Zhengui Xia, Daniel Storm, Rebecca B. Neumann
Grant Number: P42ES004696
Funding Period: 2009-2022
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Project Summary (2017-2022)

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.

This research project is working to understand the mechanisms of chemical-induced olfactory injury in Pacific salmon, and based upon the results, generate biomarkers of olfactory injury to evaluate the ecological health and remediation outcomes at Superfund sites. These studies also use zebrafish, a well-defined genetic model, to better understand the mechanisms of olfactory injury that are relevant to salmon. In this project, the researchers 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.

The researchers are using salmon and several transgenic zebrafish lines to 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. Transgenic zebrafish are also being used to evaluate the potency of other Superfund metals as olfactory toxicants. The research team is also investigating transcriptional and post-transcriptional control of olfaction during metal exposures, and to identify functionally important olfactory microRNAs (miRNAs) along with their gene targets that are essential regulators of metal-induced olfactory injury. The team is also exploring glutathione S-transferase (GST) isoforms as biomarkers of olfactory injury, and investigating the mechanisms of Nrf2 in olfactory neuroprotection.

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