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Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model

The excitatory neurotoxin domoic acid (DA) consistently contaminates food webs in coastal regions around the world. 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 bee...

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Autores principales: Hendrix, Alicia M., Lefebvre, Kathi A., Bowers, Emily K., Stuppard, Rudolph, Burbacher, Thomas, Marcinek, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143184/
https://www.ncbi.nlm.nih.gov/pubmed/37104198
http://dx.doi.org/10.3390/toxins15040259
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author Hendrix, Alicia M.
Lefebvre, Kathi A.
Bowers, Emily K.
Stuppard, Rudolph
Burbacher, Thomas
Marcinek, David J.
author_facet Hendrix, Alicia M.
Lefebvre, Kathi A.
Bowers, Emily K.
Stuppard, Rudolph
Burbacher, Thomas
Marcinek, David J.
author_sort Hendrix, Alicia M.
collection PubMed
description The excitatory neurotoxin domoic acid (DA) consistently contaminates food webs in coastal regions around the world. 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 (7–9-month-old) and aged (25–28-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–tonic 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.
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spelling pubmed-101431842023-04-29 Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model Hendrix, Alicia M. Lefebvre, Kathi A. Bowers, Emily K. Stuppard, Rudolph Burbacher, Thomas Marcinek, David J. Toxins (Basel) Article The excitatory neurotoxin domoic acid (DA) consistently contaminates food webs in coastal regions around the world. 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 (7–9-month-old) and aged (25–28-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–tonic 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. MDPI 2023-04-01 /pmc/articles/PMC10143184/ /pubmed/37104198 http://dx.doi.org/10.3390/toxins15040259 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hendrix, Alicia M.
Lefebvre, Kathi A.
Bowers, Emily K.
Stuppard, Rudolph
Burbacher, Thomas
Marcinek, David J.
Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model
title Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model
title_full Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model
title_fullStr Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model
title_full_unstemmed Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model
title_short Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model
title_sort age and sex as determinants of acute domoic acid toxicity in a mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143184/
https://www.ncbi.nlm.nih.gov/pubmed/37104198
http://dx.doi.org/10.3390/toxins15040259
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