Prenatal Exposure To Marine Toxin Causes Lasting Damage

Theresearchers saw behavioral effects of the toxin in animals afterprenatal exposure to domoic acid levels below those generally deemedsafe for adults, said Edward Levin, Ph.D. Those effects –- including anincreased susceptibility to disruptions of memory -- persisted intoadulthood, he said.

The findings in rats, therefore, imply thatthe toxin might negatively affect unborn children at levels that do notcause symptoms in expectant mothers, said Levin. While the researchersnote that eating seafood offers significant health benefits, they saidtheir findings suggest that the current threshold of toxin at whichaffected fisheries are closed should perhaps be lowered. The FederalDrug Administration (FDA) set the current limit based on levels safefor adults, Levin said.

"A single administration of domoic acidto pregnant rats had a lasting affect on the performance of theiroffspring as adults," Levin said. "The consequences are life-long.

"Thefindings suggest we may need to re-evaluate monitoring of waters,shellfish and fish to make sure that the most sensitive parts of thehuman population are protected from toxic exposure to domoic acid," hecontinued.

The researchers reported their findings in aforthcoming special issue dedicated to research on marine toxins ofNeurotoxicology and Teratology.

In 1987, more than 100 people inCanada became ill after eating cultured mussels contaminated withdomoic acid. The incident led to three deaths and memory loss inseveral others.

First detected in the U.S. on the Washingtoncoast in 1991, domoic acid is produced by microscopic algae,specifically the diatom species called Pseudo-nitzschia. When shellfishand crabs ingest the algae, the toxin can become concentrated in theirbodies.

Humans eating contaminated seafood develop symptomsincluding vomiting nausea, diarrhea and abdominal cramps. In severecases, the toxin leads to neurological damage, characterized byheadaches, confusion, coma and even death. Exposure can also causeamnesic shellfish poisoning, characterized by permanent loss ofshort-term memory.

Since the discovery of domoic acid on the WestCoast, officials there collect regular samples of affected marineanimals, including razor clams and Dungeness crabs. Fisheries areclosed when domoic acid levels reach 20 parts per million (ppm) in theanimals' tissues, the level at which the FDA deems the toxin unsafe forhuman consumption.

Earlier studies in animals have focused onlethal and highly toxic doses of domoic acid. Such exposures causeextensive damage to the hippocampus, a part of the brain involved inlearning and memory. More recent reports examining the effects of arange of doses have found highly reproducible behavioral consequencesof sublethal doses of the marine toxin, including impairments tospatial memory.

To explore the toxin's effects duringdevelopment, the Duke team administered domoic acid to pregnant rats atthree levels -- each below those found to cause convulsions or fetalloss. Others animals did not receive the toxin. The researchers thenconducted a battery of behavioral tests on the exposed and normalanimals to determine the effects of early domoic acid on movement andworking memory.

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

Toxinexposure decreased the normal difference between male and female ratsin their ability to complete tasks of spatial memory, the researchersfound. Previous research has shown that males normally outperformfemales on spatial discrimination learning in particular maze tests.

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

"Brief, low-dose domoicacid exposure in rats during gestational development results in subtleneurobehavioral impairments that persist into adolescence andadulthood," Levin said. "Furthermore, long-lasting effects on locomotoractivity and cognitive function occurred at levels having no clinicallyevident consequences for the animals."

Collaborators on the studyinclude Kristen Pizarro, Wyki Gina Pang and Jerry Harrison, all ofDuke. John Ramsdell of the NOAA-National Ocean Service also contributedto the research.