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Title: Domoic acid as a developmental neurotoxin.

Authors: Costa, Lucio G; Giordano, Gennaro; Faustman, Elaine M

Published In Neurotoxicology, (2010 Sep)

Abstract: Domoic acid (DomA) is an excitatory amino acid which can accumulate in shellfish and finfish under certain environmental conditions. DomA is a potent neurotoxin. In humans and in non-human primates, oral exposure to a few mg/kg DomA elicits gastrointestinal effects, while slightly higher doses cause neurological symptoms, seizures, memory impairment, and limbic system degeneration. In rodents, which appear to be less sensitive than humans or non-human primates, oral doses cause behavioral abnormalities (e.g. hindlimb scratching), followed by seizures and hippocampal degeneration. Similar effects are also seen in other species (from sea lions to zebrafish), indicating that DomA exerts similar neurotoxic effects across species. The neurotoxicity of DomA is ascribed to its ability to interact and activate the AMPA/KA receptors, a subfamily of receptors for the neuroexcitatory neurotransmitter glutamate. Studies exploring the neurotoxic effects of DomA on the developing nervous system indicate that DomA elicits similar behavioral, biochemical and morphological effects as in adult animals. However, most importantly, developmental neurotoxicity is seen at doses of DomA that are one to two orders of magnitude lower than those exerting neurotoxicity in adults. This difference may be due to toxicokinetic and/or toxicodynamic differences. Estimated safe doses may be exceeded in adults by high consumption of shellfish contaminated with DomA at the current limit of 20 microg/g. Given the potential higher susceptibility of the young to DomA neurotoxicity, additional studies investigating exposure to, and effects of this neurotoxin during brain development are warranted.

PubMed ID: 20471419 Exiting the NIEHS site

MeSH Terms: Animals; Environmental Exposure; Female; Humans; Kainic Acid/analogs & derivatives*; Kainic Acid/chemistry; Kainic Acid/toxicity; Male; Neurotoxicity Syndromes*/complications; Neurotoxicity Syndromes*/etiology; Neurotoxicity Syndromes*/metabolism; Neurotoxins/chemistry; Neurotoxins/toxicity*; Pregnancy; Prenatal Exposure Delayed Effects/chemically induced; Prenatal Exposure Delayed Effects/physiopathology

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