Abstract:
Human and wildlife communities depend on healthy marine environments to provide myriad resources and support. Harmful algal blooms (HABs), phenomena in which algae rapidly produce large amounts of biomass and often toxins, are becoming more frequent, widespread, and severe. This dissertation explores emerging concerns regarding domoic acid (DA), a HAB neurotoxin produced by diatoms in the genus Pseudo-nitzschia and known to cause toxicosis characterized by gastrointestinal (GI) distress, disorientation, amnesia, and mortality following consumption. The studies in chapters 2, 3, and 4 of this dissertation respectively address the potentially expanding geographic range of DA food web contamination, the interindividual susceptibilities that are of most concern for communities newly in contact with the toxin, and novel pathologies associated with new chronic exposure scenarios. Chapter 2 of this thesis describes an analysis of GI samples from four species of Alaskan ice seal over an almost 10-year period. Samples were tested for DA and regression analyses were used to assess temporal trends. We found DA in GI samples from all of the four seal species tested (bearded, ringed, spotted, and ribbon seals), and in all three regions where samples were collected (Beaufort, Chukchi, and Bering Seas). We further detected an increasing trend of DA presence over the surveyed period in samples from bearded seals in the Bering Sea. Chapter 3 employs a mouse model to follow up on early reports that advanced age is associated with increased DA sensitivity. We administered one-time, symptomatic doses of DA to adult and aged female and male mice, observed seizure-related activity for 90 minutes following exposure, and then collected tissues for analysis of persistent DA levels. We report greater toxicity in aged mice, particularly aged females, and associated greater concentrations of DA in aged and female mouse tissue at 90 minutes post exposure. Finally, Chapter 4 shifts to focus on exposure scenarios in which consumers are regularly exposed to low levels of DA, an emergent threat as DA food web contamination becomes more ubiquitous. We exposed adult and aged female mice to 0.5 mg/kg bw DA thrice weekly for 14 weeks, assessed activity-related outcomes in Phenotyper cages, and then allowed a 10-week washout period before repeating tests. We also opportunistically measured cardiac function by echocardiography post exposure and again post washout. We found that DA exposure was associated with high mortality in aged mice, and with hyperactivity in adult mice, which did not appear to be significantly affected by washout. We found similar mild persistent effects of low dose DA on diastolic cardiac function. Collectively, these experiments contribute to the body of knowledge that informs effective protective measures for seafood consumers moving forward; we have identified geographic regions newly subject to DA threats, members of the population at greater risk for the health effects of exposure, and both behavioral and cardiac pathways impacted by novel repeated, low-level exposure scenarios.