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Effects and Discovery of Chronic Domoic Acid Exposure on Gene Expression in the Vertebrate Central Nervous System

This project began in January 2009 and was completed in December 2012

Domoic acid, a naturally occurring marine neurotoxin, threatens the health of marine mammals, seabirds, and humans via severe and long-term yet low-level exposure through the food web. Researchers discovered a biomarker of chronic exposure to domoic acid in fish and in naturally exposed sea lions. This marker will help scientists assess the effects of low level, chronic domoic acid exposure on human health.

Why We Care
The potential impacts of chronic algal toxin exposure remain a long running health concern. One harmful algal bloom (HAB) toxin, domoic acid (DA), is a potent neurotoxin naturally produced by several species of the algal diatom genus Pseudo-nitzschia. DA usually transfers to higher trophic level animals via filter feeding bivalves or fish, exposing many vertebrate species including marine mammals, birds, and even humans. The clinical signs of acute (severe) DA toxicity, well defined as amnesic shellfish poisoning, result in severe illness and sometimes death. However, virtually nothing is known about the impacts of chronic (long-term, low-level) toxin exposure, primarily due to the difficulties associated with long-term exposure studies. Further, since DA is not detectable in the body for long after initial exposure, determining whether organisms have experienced chronic exposure remain difficult.

What We Did
Our objectives were to:

  1. quantify changes in gene expression (the number and types of genes present) in the vertebrate central nervous system and characterize the expressed genes to identify the potential pathways of disease and identify biomarkers associated with long-term, low-level (i.e., chronic) DA exposure,
  2. quantify blood toxin levels associated with these changes in gene expression, and
  3. examine changes in tissues of all major organ systems to characterize impacts of chronic toxicity.

We used the “toxicogenetic” approach (genetic influences on the responses of organisms to toxins) applying gene technology. Our efforts quantified gene expression in whole brain during a one-year DA exposure study using a surrogate vertebrate model (the laboratory zebrafish, Danio rerio). Chronic, low-level exposure to DA induced an antibody response and increased sensitivity to the toxin in zebrafish. This project is part of the Ecology and Oceanography of Harmful Algal Blooms (ECOHAB) program.

What We Found
Using the “toxicogenetic” approach of studying genetic influences on the responses of organisms to toxins, we found a novel DA-specific antibody response that signifies chronic low-level exposure in zebrafish. This means we can now look for this DA-specific antibody to represent exposure levels (a biomarker) that could help with diagnosis and treatment in both marine mammal and human populations.

Benefits of Our Work
This was the first investigation to comprehensively define the impacts of chronic, low-level algal toxin exposure using a realistic long-term exposure time scale. Our discovery of the antibody response has profound implications for the development of diagnostic tests for exposure to DA and other pervasive environmental toxins. These results led to new, extended research that better assesses health risks in mammals including in at risk human consumers of DA-contaminated seafood.

The project was led by Dr. Kathi Lefebvre of the NOAA National Marine Fisheries Service Northwest Fisheries Science Center in partnership with Drs. Richard Beyer, Frederico Farin, and Theo Bammler of the University of Washington Department of Environmental and Occupational Health Sciences along with Mark Meyers of the NOAA Northwest Fisheries Science Center.

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