title: A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity.
abstract: The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.
authors.affiliation: Exposure Assessment and Biomedical Models, Northwest Fisheries Science Center, National Marine Fisheries Service, NOAA, Seattle, Washington, United States of America. Kathi.Lefebvre@noaa.gov
authors.forename: Kathi A
authors.initials: KA
authors.lastname: Lefebvre
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Frame
authors.forename: Frances
authors.initials: F
authors.lastname: Gulland
authors.forename: John D
authors.initials: JD
authors.lastname: Hansen
authors.forename: Preston S
authors.initials: PS
authors.lastname: Kendrick
authors.forename: Richard P
authors.initials: RP
authors.lastname: Beyer
authors.forename: Theo K
authors.initials: TK
authors.lastname: Bammler
authors.forename: Frederico M
authors.initials: FM
authors.lastname: Farin
authors.forename: Emma M
authors.initials: EM
authors.lastname: Hiolski
authors.forename: Donald R
authors.initials: DR
authors.lastname: Smith
authors.forename: David J
authors.initials: DJ
authors.lastname: Marcinek
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism*; D006801:Humans; D007608:Kainic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology; D008387:Marine Toxins / Q000276:immunology*; D046070:Sea Lions / Q000276:immunology*; D015027:Zebrafish / Q000276:immunology*
chemical_list: D015415:Biomarkers; D008387:Marine Toxins; C012301:domoic acid; D007608:Kainic Acid