Zebrafish seizure model identifies p,p -DDE as the dominant contaminant of fetal California sea lions that accounts for synergistic activity with domoic acid.
BACKGROUND
Fetal poisoning of California sea lions (CSLs; Zalophus californianus) has been associated with exposure to the algal toxin domoic acid. These same sea lions accumulate a mixture of persistent environmental contaminants including pesticides and industrial products such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Developmental exposure to the pesticide dichlorodiphenyltrichloroethane (DDT) and its stable metabolite 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (p,p -DDE) has been shown to enhance domoic acid-induced seizures in zebrafish; however, the contribution of other co-occurring contaminants is unknown.


OBJECTIVE
We formulated a mixture of contaminants to include PCBs, PBDEs, hexachlorocyclohexane (HCH), and chlordane at levels matching those reported for fetal CSL blubber to determine the impact of co-occurring persistent contaminants with p,p -DDE on chemically induced seizures in zebrafish as a model for the CSLs.


METHODS
Embryos were exposed (6-30 hr postfertilization) to p,p -DDE in the presence or absence of a defined contaminant mixture prior to neurodevelopment via either bath exposure or embryo yolk sac microinjection. After brain maturation (7 days postfertilization), fish were exposed to a chemical convulsant, either pentylenetetrazole or domoic acid; resulting seizure behavior was then monitored and analyzed for changes, using cameras and behavioral tracking software.


RESULTS
Induced seizure behavior did not differ significantly between subjects with embryonic exposure to a contaminant mixture and those exposed to p,p -DDE only.


CONCLUSIONS
These studies demonstrate that p,p -DDE--in the absence of PCBs, HCH, chlordane, and PBDEs that co-occur in fetal sea lions--accounts for the synergistic activity that leads to greater sensitivity to domoic acid seizures.
Tiedeken
Jessica A
JA
Marine Biotoxins Program, Center for Coastal Environmental Health and Biomolecular Research, National Oceanic and Atmospheric Administration, National Ocean Service, Charleston, South Carolina 29412, USA. john.ramsdell@noaa.gov
Ramsdell
John S
JS
D000818:Animals; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D004195:Disease Models, Animal; D004785:Environmental Pollutants / Q000633:toxicity*; D005333:Fetus / Q000187:drug effects; D055768:Halogenated Diphenyl Ethers; D001556:Hexachlorocyclohexane / Q000633:toxicity; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced*; D015027:Zebrafish
D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D003633:Dichlorodiphenyl Dichloroethylene; D001556:Hexachlorocyclohexane; D011078:Polychlorinated Biphenyls; C012301:domoic acid; D007608:Kainic Acid