Low-Level Domoic Acid Exposure Induces Age-like Cardiomyopathy in Young Adult and Aged Mice

Domoic acid (DA) is a well-known seafood toxin produced by some species of marine phytoplankton in the genus Pseudo-nitzschia during harmful algal blooms (HABs). Acute toxic exposures induce overt clinical signs of neuroexcitotoxicity, such as seizures in mammals due to overstimulation of glutamate receptors in the central nervous system (CNS). Acute DA excitotoxicity via the CNS has been well-studied in both field poisoning events and laboratory exposure studies with rodent models, but little is known about the impacts of low-level DA exposures below those that cause outward signs of neurotoxicity; the impacts on other potential target organs, including the heart; or age-related sensitivities. Here, low-level DA exposures in young adult (9 mo) and old (24 mo) mice were conducted over multiple weeks. Mortality, cardiac function, frailty, and protein expression were quantified to assess age-related DA sensitivity and potential impacts on heart function. Echocardiography and proteome data confirm that chronic low-level DA exposure causes irreversible functional cardiomyopathy and protein remodeling in young adult mice that mimics natural cardiac aging. In addition, old mice exhibit higher mortality and frailty than young adult mice with the same low-level DA exposures. These results provide critical information for assessing potential health risks to humans who regularly consume seafood with low levels of DA.