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Acute exposure to the toxin causes Amnesic Shellfish Poisoning, a potentially lethal syndrome of gastrointestinal- and seizure-related outcomes. Both advanced age and male sex have been suggested to contribute to interindividual DA susceptibility. To test this, we administered DA doses between 0.5 and 2.5 mg\/kg body weight to female and male C57Bl\/6 mice at adult (7\u20139-month-old) and aged (25\u201328-month-old) life stages and observed seizure-related activity for 90 min, at which point we euthanized the mice and collected serum, cortical, and kidney samples. We observed severe clonic\u2013tonic convulsions in some aged individuals, but not in younger adults. We also saw an association between advanced age and the incidence of a moderately severe seizure-related outcome, hindlimb tremors, and between advanced age and overall symptom severity and persistence. Surprisingly, we additionally report that female mice, particularly aged female mice, demonstrated more severe neurotoxic symptoms following acute exposure to DA than males. Both age and sex patterns were reflected in tissue DA concentrations as well: aged mice and females had generally higher concentrations of DA in their tissues at 90 min post-exposure. This study contributes to the body of work that can inform intelligent, evidence-based public health protections for communities threatened by more frequent and extensive DA-producing algal blooms.<\/jats:p>","DOI":"10.3390\/toxins15040259","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T02:10:13Z","timestamp":1680487813000},"page":"259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3897-1788","authenticated-orcid":false,"given":"Alicia M.","family":"Hendrix","sequence":"first","affiliation":[{"name":"Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1036-3740","authenticated-orcid":false,"given":"Kathi A.","family":"Lefebvre","sequence":"additional","affiliation":[{"name":"Environmental Fisheries Science Division, Northwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, Seattle, WA 98112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily K.","family":"Bowers","sequence":"additional","affiliation":[{"name":"Environmental Fisheries Science Division, Northwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, Seattle, WA 98112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph","family":"Stuppard","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Washington School of Medicine, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Burbacher","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5187-2149","authenticated-orcid":false,"given":"David J.","family":"Marcinek","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Washington School of Medicine, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.algal.2015.11.020","article-title":"Environmental Roles and Biological Activity of Domoic Acid: A Review","volume":"13","author":"Zabaglo","year":"2016","journal-title":"Algal Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3390\/md6020180","article-title":"Domoic Acid Toxicologic Pathology: A Review","volume":"6","author":"Pulido","year":"2008","journal-title":"Mar. 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Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"107865","DOI":"10.1016\/j.pharmthera.2021.107865","article-title":"Public Health Risks Associated with Chronic, Low-Level Domoic Acid Exposure: A Review of the Evidence","volume":"227","author":"Petroff","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.envint.2017.01.006","article-title":"Acute and Chronic Dietary Exposure to Domoic Acid in Recreational Harvesters: A Survey of Shellfish Consumption Behavior","volume":"101","author":"Ferriss","year":"2017","journal-title":"Environ. Int."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zheng, G., Wu, H., Che, H., Li, X., Zhang, Z., Peng, J., Guo, M., and Tan, Z. (2022). Residue Analysis and Assessment of the Risk of Dietary Exposure to Domoic Acid in Shellfish from the Coastal Areas of China. 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