Harmful blooms of domoic acid-producing algae are a growing problem. Species affected include some that are threatened or endangered. Humans are at risk, and consequences can be severe. Despite established seafood testing mechanisms, concerns about potential human exposures persist, including in utero exposure, which might go undetected initially but have detrimental long-term consequences. Previous rodent studies suggest in utero exposure to domoic acid might cause neuropathological changes in the hippocampus and the development of epilepsy, but direct evidence of spontaneous seizures is lacking. The investigators will attempt to fill this critical gap. The proposed project is an interdisciplinary collaboration among wildlife veterinarians and biomedical scientists to test the hypothesis that in utero exposure to domoic acid causes temporal lobe epilepsy, albeit a milder form than that caused by adult exposure.
Aim 1 is to test whether in utero exposure to domoic acid causes temporal lobe epilepsy in mice and to compare the neuropathology to that of mice exposed as adults.
Aim 2 is to test the hypothesis in California sea lions by evaluating brain tissue from animals euthanized because of domoic acid toxicosis with a poor prognosis. Results will indicate whether or not in utero exposure can cause temporal lobe epilepsy to develop, and if so, whether it is as severe as that which develops after adult exposure. Findings will inform future decisions on whether and how to further evaluate risks of in utero exposure to domoic acid in humans. In addition, Aim 2 will generate rare, perfusion-fixed, quantitative whole-brain data from animals that have a large, gyrencephalic brain and naturally occurring temporal lobe epilepsy, which could provide insight into mechanisms of epileptogenesis.

Public Health Relevance

The proposed project addresses growing concerns that human embryos might be at risk when pregnant women consume seafood containing naturally occurring toxins at levels below current regulatory limits. The investigators will determine whether or not exposure during pregnancy can cause temporal lobe epilepsy in laboratory mice and naturally exposed sea lions.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Special Emphasis Panel (ZES1)
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Tyson, Frederick L
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Stanford University
Veterinary Sciences
Schools of Medicine
United States
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Buckmaster, Paul S; Wen, Xiling; Toyoda, Izumi et al. (2014) Hippocampal neuropathology of domoic acid-induced epilepsy in California sea lions (Zalophus californianus). J Comp Neurol 522:1691-706