# Increased Risk of Chronic Disease Due to Domoic Acid Exposure with Age

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $130,563

## Abstract

ABSTRACT
The proposal is based on a new exposure paradigm for seafood toxin domoic acid (DA) where we have
identified significant learning deficits in a laboratory models associated with sub-clinical chronic DA exposure.
This is significant because exposure risks to DA are increasing as harmful algal blooms continue to increase in
magnitude, duration and geographic expanse due to warming ocean conditions. It is well known that DA is a
potent excitotoxin with severe effects on the central nervous system leading to seizures and death with acute
exposure in both human and wildlife seafood consumers. Laboratory studies and diagnostics of DA exposed
marine mammals have further documented permanent impacts on cognitive, cardiac and renal systems. The
human health risks of acute exposure have been minimized with the implementation of the current seafood
regulatory limit of 20 ug DA/g seafood based on an acute reference dose (ARfD) for a single exposure
designed to prevent seizures. However, the ARfD does not take into account subclinical effects, repetitive
exposure, and effects of age on DA susceptibility. Recent seafood consumption studies by our team revealed
that some recreational harvesters exceeded the ARfD and/or were chronically exposed to DA weekly for at
least six consecutive months and that the majority of this group is over 60 years of age. Aging is the single
greatest risk factor for multiple chronic diseases, including those affecting cognitive, cardiac, and renal
function, all of which are also targets of DA toxicity. There is a critical need to understand how the interaction
between DA exposure and aging contributes to the risk of chronic disease and toxin susceptibility as DA
becomes more persistent in seafood resources. To address this knowledge gap in aims 1 & 2, we will test
whether aging increases susceptibility to toxicity from acute symptomatic and chronic low-level asymptomatic
DA exposures as well as persistence of toxic effects in young and old mice by quantifying tissue pathology and
dysfunction in cognitive, cardiac and renal systems. Our preliminary data indicate that long-term low-level DA
exposure affects mitochondrial function in these systems. In aim 3 we will test the hypothesis that
mitochondrial oxidative stress underlies chronic DA toxicity in cognitive, cardiac and renal systems using a
transgenic mouse model (mCAT) that overexpresses catalase, a key antioxidant enzyme in the mitochondria.
Results from this study will unambiguously provide new mechanistic insights into how low level subclinical
chronic exposures can affect healthspan and contribute to chronic disease as well as point to whether new
mitochondrial targeted interventions may be effective at reducing DA exposure health risks.

## Key facts

- **NIH application ID:** 10438785
- **Project number:** 5R01ES030319-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** David J. Marcinek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $130,563
- **Award type:** 5
- **Project period:** 2018-09-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438785

## Citation

> US National Institutes of Health, RePORTER application 10438785, Increased Risk of Chronic Disease Due to Domoic Acid Exposure with Age (5R01ES030319-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10438785. Licensed CC0.

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