Blooms of domoic acid (DA)-producing Pseudo-nitzschia species, responsible for a neurologic illness know as amnesic shellfish poisoning (ASP), occur throughout the worlds oceans and are exceptionally frequent in local coastal waters. Acute exposure to DA is known to cause severe behavioral neurotoxicity and death in many vertebrate species such as humans, marine mammals, seabirds, and fish, yet little is known about chronic effects of low-level exposure. In order to accurately assess public health risks related to harmful algal bloom toxins an understanding of chronic exposure effects, susceptibility, and toxin sensitivity is imperative. The proposed research will utilized the zebrafish model system to identify biomarkers of DA toxicity in the vertebrate central nervous system expressed during exposure in both early developmental and adult stages. Due to the conserved genomics of major developmental cell signaling and response pathways in vertebrate systems, zebrafish are widely recognized as a useful model for studying human disease. Current evidence suggests that two such pathways, oxidative stress and apoptotic processes, are likely involved in DA neurotoxicity. The induction and effects of both pathways may be markedly different during periods of early development and adulthood making certain ages more sensitive to DA than others. Early developmental stages may have increased susceptibility due to decreased antioxidant capacity and a high level of sensitive developmental neurogenesis and apoptotic processes in the CNS. The proposed model will be used to identify and determine toxin levels at which chronic effects occur in both adult and early developmental stages to assess age-

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Specialized Center (P50)
Project #
5P50ES012762-05
Application #
7569498
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
2008-01-01
Budget End
2008-12-31
Support Year
5
Fiscal Year
2008
Total Cost
$7,826
Indirect Cost
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Bender, Sara J; Parker, Micaela S; Armbrust, E Virginia (2012) Coupled effects of light and nitrogen source on the urea cycle and nitrogen metabolism over a diel cycle in the marine diatom Thalassiosira pseudonana. Protist 163:232-51

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