Prenatal Exposure to Marine Toxin Causes Lasting Damage

Duke University Medical Center researchers have found that the naturally occurring marine toxin domoic acid can cause subtle but lasting cognitive damage in rats exposed to the chemical before birth. Humans can become poisoned by the potentially lethal, algal toxin after eating contaminated shellfish.

The researchers saw behavioral effects of the toxin in animals after prenatal exposure to domoic acid levels below those generally deemed safe for adults, said Edward Levin, Ph.D. Those effects –- including an increased susceptibility to disruptions of memory — persisted into adulthood, he said.

The findings in rats, therefore, imply that the toxin might negatively affect unborn children at levels that do not cause symptoms in expectant mothers, said Levin. While the researchers note that eating seafood offers significant health benefits, they said their findings suggest that the current threshold of toxin at which affected fisheries are closed should perhaps be lowered. The Federal Drug Administration (FDA) set the current limit based on levels safe for adults, Levin said.

“A single administration of domoic acid to pregnant rats had a lasting affect on the performance of their offspring as adults,” Levin said. “The consequences are life-long.

“The findings suggest we may need to re-evaluate monitoring of waters, shellfish and fish to make sure that the most sensitive parts of the human population are protected from toxic exposure to domoic acid,” he continued.

The researchers reported their findings in a forthcoming special issue dedicated to research on marine toxins of Neurotoxicology and Teratology.

In 1987, more than 100 people in Canada became ill after eating cultured mussels contaminated with domoic acid. The incident led to three deaths and memory loss in several others.

First detected in the U.S. on the Washington coast in 1991, domoic acid is produced by microscopic algae, specifically the diatom species called Pseudo-nitzschia. When shellfish and crabs ingest the algae, the toxin can become concentrated in their bodies.

Humans eating contaminated seafood develop symptoms including vomiting nausea, diarrhea and abdominal cramps. In severe cases, the toxin leads to neurological damage, characterized by headaches, confusion, coma and even death. Exposure can also cause amnesic shellfish poisoning, characterized by permanent loss of short-term memory.

Since the discovery of domoic acid on the West Coast, officials there collect regular samples of affected marine animals, including razor clams and Dungeness crabs. Fisheries are closed when domoic acid levels reach 20 parts per million (ppm) in the animals’ tissues, the level at which the FDA deems the toxin unsafe for human consumption.

Earlier studies in animals have focused on lethal and highly toxic doses of domoic acid. Such exposures cause extensive damage to the hippocampus, a part of the brain involved in learning and memory. More recent reports examining the effects of a range of doses have found highly reproducible behavioral consequences of sublethal doses of the marine toxin, including impairments to spatial memory.

To explore the toxin’s effects during development, the Duke team administered domoic acid to pregnant rats at three levels — each below those found to cause convulsions or fetal loss. Others animals did not receive the toxin. The researchers then conducted a battery of behavioral tests on the exposed and normal animals to determine the effects of early domoic acid on movement and working memory.

Rats with a history of domoic acid exposure showed greater initial activity in a maze test than control rats, followed by a rapid decline. Moreover, domoic acid exposure affected cognitive function in complex ways, the researchers reported.

Toxin exposure decreased the normal difference between male and female rats in their ability to complete tasks of spatial memory, the researchers found. Previous research has shown that males normally outperform females on spatial discrimination learning in particular maze tests.

Exposed rats of both sexes also showed greater susceptibility to a chemical that induces amnesia by compromising particular brain receptors, suggesting that the animals had less functional reserve with which to solve memory tasks, the researchers said.

“Brief, low-dose domoic acid exposure in rats during gestational development results in subtle neurobehavioral impairments that persist into adolescence and adulthood,” Levin said. “Furthermore, long-lasting effects on locomotor activity and cognitive function occurred at levels having no clinically evident consequences for the animals.”

Collaborators on the study include Kristen Pizarro, Wyki Gina Pang and Jerry Harrison, all of Duke. John Ramsdell of the NOAA-National Ocean Service also contributed to the research.