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Epileptic Disease Origins in the California Sea Lion

This project began in January 2002 and was completed in December 2013

The womb is normally viewed as a protective environment. Sometimes drugs or toxicants can harm the fetus, even without apparent effects on the mother. A 2002 domoic acid (DA) producing algal bloom caused a poisoning event at the Channel Island’s National Marine Sanctuary, leading to deaths of nearly 200 fetal California sea lions. We measured high levels of DA in both mothers and fetuses providing an opportunity to understand if fetuses are at greater risk of poisoning and impact on survivors.

Why We Care
The occurrence of DA poisoning events has become an annual event on the west coast of the United States. Previous research observed that hundreds of sea lions were showing signs of DA poisoning when no evidence of the harmful algal bloom (HAB) was apparent. Adult females were the most likely to be acutely poisoned when DA was present, but young animals were most commonly showing signs of a chronic disease in the absence of DA. This prompted us to look at possible in utero (in the womb) exposure as a mechanism for this chronic disease state.

Our previous findings show that animals can continue to have epilepsy and aggressive behaviors weeks to months after DA poisoning. It is believed that this phenomenon—known as the fetal basis to adult disease—now seen in sea lions, is very likely due to exposure to the algal toxin before birth. This is due to greater exposure that occurs in the in utero environment and the long pregnancy of the sea lion. However, this hypothesis required experimental evidence to affect science based decision making.

What We Did
We first determined how domoic acid (DA) transfers to the fetus in laboratory rats. These experiments showed the toxin transferred from maternal to fetal blood and accumulated in amniotic fluid. We performed a first-of-its-kind analysis of domoic acid poisoning during fetal brain development in partnership with the California Marine Mammal Center. We developed a linkage between the commonly studied laboratory rat and the California sea lion. We also revealed how the day of the year could predict the stage of brain development in fetal sea lions.

We analyzed the risk of epilepsy that develops from fetal exposure of DA and provided a projection of the outcome of fetal poisoning based upon the date of the bloom occurrence. Still needing to understand the threshold for disease, we conducted a study to determine the rate DA enters the fetus and its fate in the body (toxicokinetic parameters). This determined how much of the mother’s toxin is transferred to the fetus  and that the fetus is at much higher risk because, unlike the mother, the toxin is slow to exit the fetus brain.

Next Steps
This information has been disseminated broadly through official NOAA press releases, articles in the press and through formal and informal communications. As an example, in the summer of 2011 this information was used to help zoo veterinarians who had received rescued sea lion pups only to find months later they were exhibiting signs of epilepsy.

The occurrence and extent of algal blooms change with short and long term weather patterns, so teams of scientists across the U.S. continue improving monitoring, forecasting and predicting HABs. Our toxicologists apply multiple data streams to develop improved models that predict the long term impact of algal toxins on populations of high risk and high concern. With mutual commitment, NOAA and its partners work to better understand the long-term effects of HABs. We strive to provide useful methods to forecast fetal toxicity and understand the impact of fetal toxicity on adult disease in California sea lion populations.

Additional Resources

Click to expand resource list(s).

Peer-Reviewed Publications

  • Ramsdell, J.S. 2010. Neurological Disease Rises from Ocean to Bring Model for Human Epilepsy to Life. Toxins 2(7):1646–1675.
  • Ramsdell, J.S. and T.S. Zabka. 2008. In Utero Domoic Acid Toxicity: A Fetal Basis to Adult Disease in the California Sea Lion (Zalophus californianus). Marine Drugs 6(2):262–290.
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