Algae of the Pseudo-nitzschia genus are found in marine environments worldwide. Harmful blooms of Pseudo-nitzschia produce domoic acid that contaminates marine food webs and affects many species. People are at risk of domoic acid toxicosis and consequences can be severe, including amnesia and seizures. In adult animals domoic acid exposure can cause status epilepticus, excitotoxic neuron loss, aberrant synaptic reorganization, and temporal lobe epilepsy. In utero exposure to domoic acid in rodents causes long-term behavioral impairments, epileptiform EEG activity, and reduced seizure threshold. Morphological abnormalities also occur, especially in the hippocampus, but changes are milder than those caused by domoic acid exposure in adults. Evidence from California sea lions (Zalophus californianus) suggests natural exposure to domoic acid in utero might cause later development of temporal lobe epilepsy. These findings have raised growing concern that human embryos might be at risk when pregnant women consume seafood containing domoic acid at levels below current regulatory limits.

In this project, a research team at Stanford University will conduct experiments 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. There are two overall objectives: (1) to determine 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; and (2) to test the hypothesis in California sea lions by evaluating brain tissue from animals euthanized because of domoic acid toxicosis with a poor prognosis.

This research will address growing concerns that human embryos might be at risk when pregnant women consume seafood containing domoic acid at levels below current regulatory limits. Results will determine whether or not in utero exposure to domoic acid causes epilepsy in mice and perhaps in sea lions. If results of the proposed proof-of-concept experiments support the hypothesis that in utero exposure to domoic acid causes temporal lobe epilepsy, they will provide rationale for investing in further studies to more directly evaluate risks to humans. Furthermore, if in utero exposure to domoic acid causes epilepsy in mice and sea lions, results generated will reveal the pattern and extent of associated brain damage, which might help identify underlying epileptogenic circuit anomalies.

Broader Impacts. Trainees will participate in the proposed project. They include a graduate student and veterinary students that come to Stanford University for the summer to gain research experience through an NIH-funded training grant (T35 OD010989). They will learn about epilepsy, environmental exposure to toxins, comparative neuroanatomy, and EEG recording .

JOINT FUNDING BY NSF AND NIEHS: The original proposal on which this project is based (R01 ES021960-01) was submitted to the National Institutes of Environmental Health Sciences (NIH/NIEHS) in response to Funding Opportunity Announcement RFA-ES-11-013 , "Oceans, Great Lakes and Human Health (R01)", an opportunity jointly sponsored by NSF. This project is cooperatively funded through separate awards from NSF and NIEHS.

Agency
National Science Foundation (NSF)
Institute
Division of Ocean Sciences (OCE)
Application #
1313821
Program Officer
Donald L. Rice
Project Start
Project End
Budget Start
2013-02-01
Budget End
2018-01-31
Support Year
Fiscal Year
2013
Total Cost
$467,592
Indirect Cost
Name
Stanford University
Department
Type
DUNS #
City
Palo Alto
State
CA
Country
United States
Zip Code
94304