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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/15/4/259 |
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| author | Alicia M. Hendrix Kathi A. Lefebvre Emily K. Bowers Rudolph Stuppard Thomas Burbacher David J. Marcinek |
| author_facet | Alicia M. Hendrix Kathi A. Lefebvre Emily K. Bowers Rudolph Stuppard Thomas Burbacher David J. Marcinek |
| author_sort | Alicia M. Hendrix |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T04:28:08Z |
| format | Article |
| id | doaj.art-7e6279913e614833a411423855995121 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-11T04:28:08Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-7e6279913e614833a4114238559951212023-11-17T21:38:41ZengMDPI AGToxins2072-66512023-04-0115425910.3390/toxins15040259Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse ModelAlicia M. Hendrix0Kathi A. Lefebvre1Emily K. Bowers2Rudolph Stuppard3Thomas Burbacher4David J. Marcinek5Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USAEnvironmental Fisheries Science Division, Northwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, Seattle, WA 98112, USAEnvironmental Fisheries Science Division, Northwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, Seattle, WA 98112, USADepartment of Radiology, University of Washington School of Medicine, Seattle, WA 98195, USADepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USADepartment of Radiology, University of Washington School of Medicine, Seattle, WA 98195, USAThe 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.https://www.mdpi.com/2072-6651/15/4/259domoic acidagingseizuresexcitotoxicityamnesic shellfish poisoning |
| spellingShingle | Alicia M. Hendrix Kathi A. Lefebvre Emily K. Bowers Rudolph Stuppard Thomas Burbacher David J. Marcinek Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model Toxins domoic acid aging seizures excitotoxicity amnesic shellfish poisoning |
| 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 | domoic acid aging seizures excitotoxicity amnesic shellfish poisoning |
| url | https://www.mdpi.com/2072-6651/15/4/259 |
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