There is a critical knowledge gap regarding the impacts of chronic low-level exposure to common environmental toxins such as the neurotoxic amino acid, domoic acid (DA), a phycotoxin naturally produced during harmful algal blooms (HABs). Accumulation of DA 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. In fact, recent findings b a member of this investigative team suggest that significant cognitive impairment and increased seizure prevalence occur in a coastal cohort of shellfish consumers compared to non-consumers of DA-containing shellfish. The subclinical health effects and underlying mechanisms of chronic toxicity are difficult to elucidate primarily due to the lack of a biomarker specific for chronic exposure. The investigators' research team has discovered 1) a novel antibody based biomarker that is a specific signature for chronic low-level DA exposure, and 2) that chronic exposure increases toxin susceptibility in subsequent exposures in a zebrafish chronic exposure model. Here they test the hypothesis that a DA- specific antibody is a persistent biomarker for low-level chronic exposure that results in neurotoxicity even in the absence of the overt neurobehavioral symptoms characteristic of acute exposure. The investigators have detected the antibody biomarker in naturally DA-exposed California sea lions, thereby ensuring that the antibody response occurs in mammals under environmentally relevant exposure conditions. The overall goals of the study are to 1) develop and validate a biomarker for chronic low-level exposure to DA, 2) link this biomarker to quantifiable subclinical neurotoxic logical endpoints, and 3) quantify the effects of chronic exposure on overall whole animal toxin susceptibility (i.e., increased sensitivity or resistance) in a mammalian model system. This is the first solid 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.

Public Health Relevance

Chronic exposure to low levels of the algal toxin domoic acid may pose significant health threats to human and wildlife populations that regularly consume domoic acid contaminated seafood. This research team has discovered an antibody response that is a specific biomarker for chronic domoic acid exposure and proposes to use mouse model to further identify toxic health impacts that can be linked to antibody levels. Results from this stud would provide the first diagnostic test for chronic exposure for use in human and wildlife health assessments.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Special Emphasis Panel (ZES1)
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Tyson, Frederick L
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University of Washington
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Moyer, Caitlin E; Hiolski, Emma M; Marcinek, David J et al. (2018) Repeated low level domoic acid exposure increases CA1 VGluT1 levels, but not bouton density, VGluT2 or VGAT levels in the hippocampus of adult mice. Harmful Algae 79:74-86
Lefebvre, Kathi A; Hendrix, Alicia; Halaska, Barbie et al. (2018) Domoic acid in California sea lion fetal fluids indicates continuous exposure to a neuroteratogen poses risks to mammals. Harmful Algae 79:53-57
Lefebvre, Kathi A; Kendrick, Preston S; Ladiges, Warren et al. (2017) Chronic low-level exposure to the common seafood toxin domoic acid causes cognitive deficits in mice. Harmful Algae 64:20-29
Ferriss, Bridget E; Marcinek, David J; Ayres, Daniel et al. (2017) Acute and chronic dietary exposure to domoic acid in recreational harvesters: A survey of shellfish consumption behavior. Environ Int 101:70-79
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Hiolski, Emma M; Kendrick, Preston S; Frame, Elizabeth R et al. (2014) Chronic low-level domoic acid exposure alters gene transcription and impairs mitochondrial function in the CNS. Aquat Toxicol 155:151-9
Lefebvre, Kathi A; Frame, Elizabeth R; Gulland, Frances et al. (2012) A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity. PLoS One 7:e36213