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

University Of Washington, Seattle WA

Investigators

Abstract

Domoic acid (DA) is a toxin produced by a type of harmful algal bloom. Domoic acid accumulates in seafood products and can harm marine mammals and humans who consume contaminated shellfish. At high doses, DA is responsible for the neurotoxic illness known as amnesic shellfish poisoning (ASP), with clinical symptoms that include seizures, memory loss, coma, and death. The effects of chronic exposure to lower doses are less well understood. Recent seafood consumption studies by this research team revealed that some recreational harvesters exceeded the current regulated dose limit 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 brain, heart, and kidney function, all of which are also targets of DA toxicity. This study will investigate how the effects of domoic acid exposure change with age. As ocean conditions change, exposure to DA through seafood consumption is likely to increase as a result of increased frequency and severity of toxin producing blooms. Thus a better understanding of the effect of DA exposure on the risk of developing chronic disease and the mechanisms underlying long term health problems, especially in the elderly population, is critical for better management of these risks by regulatory bodies and improved communication with stakeholders. The research is jointly supported by NSF and by the National Institute for Environmental Health Sciences (NIEHS). The study has three specific aims. First, in order to test the hypothesis that aging increases susceptibility to acute DA toxicity the investigators will measure the effects of acute symptomatic DA exposure on cognitive, cardiac and renal function in young and old mice. Following an acute symptomatic exposure, they will quantify tissue pathology and dysfunction in three systems with known DA induced pathology - cognitive, cardiac, and kidney systems. Second, in order to test the hypothesis that aging increases the susceptibility to chronic DA toxicity they will measure the effects of chronic low-level DA exposure on cognitive, cardiac and renal function in young and old mice. The investigators have previously demonstrated that chronic low-level DA exposure caused reversible cognitive deficits. However, whether aging affects the susceptibility to and reversibility of chronic DA toxicity to cognitive, cardiac and renal function has not been examined. Finally, in order to test the hypothesis that mitochondrial oxidative stress underlies chronic DA toxicity in cognitive, cardiac and renal systems they will use the chronic DA exposure paradigm (aim 2) in a mouse model (mCAT) overexpressing catalase, a key antioxidant enzyme, in the mitochondria. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.