Accumulation of the neurotoxic amino acid domoic acid (DA), a phycotoxin naturally produced during harmful algal blooms (HABs), in the food web poses significant health threats to humans and wildlife and is responsible for a neurotoxic illness known as amnesic shellfish poisoning (ASP). Regular monitoring of DA levels in edible shellfish tissues has been effective in protecting human consumers from acute high-level DA exposure. However, there is no protection from chronic low-level DA exposure, which may pose significant human health risks, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Due to increasing algal toxin exposure threats globally, there is a critical need for rapid and reliable diagnostic tests for assessing chronic DA exposure in human and wildlife populations, and for evidence that clearly establishes the relationship between chronic DA exposure, biomarker response, and health impacts.
In this proposal a research team led by a scientist at the University of Washington will test the hypothesis that the presence of a DA-specific antibody is a biomarker for chronic low-level exposure that can be linked to subclinical health impacts in a mouse model system. Recently, this team has discovered (1) a novel antibody based biomarker that is a specific signature for chronic low-level DA exposure and pathology, and (2) that chronic exposure increases toxin susceptibility in subsequent exposures in a zebrafish chronic exposure model. In study the specific objectives are (1) to test the timing and duration of the antibody response following chronic, low-level DA exposure in mice, (2) to determine whether this response is indicative of subclinical neurotoxicity, and (3) to test whether previous exposures to DA affect subsequent toxic susceptibility. The new insight will be whether the presence of a DA-specific antibody is a reliable indicator of previously undetectable chronic DA exposures, and in turn an accurate predictor of significant health effects.
Broader Impacts: Chronic, low-level exposure to DA is a genuine concern for members of coastal and tribal communities who routinely harvest and consume shellfish. Currently, the only way to assess exposure in humans is through shellfish consumption surveys. This study will be an important first step towards developing a viable diagnostic test for assessing health impacts of chronic low-level DA exposure and will be an important tool for monitoring changes in exposure risks associated with changing ocean conditions.
JOINT FUNDING BY NSF AND NIEHS: The original proposal on which this project is based (R01 ES021930-01) was submitted to the National Institutes of Environmental Health Sciences (NIH/NIEHS) in response to Funding Opportunity Announcement RFA-ES-11-013 , "Oceans, Great Lakes and Human Health (R01)", an opportunity jointly sponsored by NSF. This project is cooperatively funded through separate awards from NSF and NIEHS.
