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Neuropathology of excitatory neurotoxins: the domoic acid model
1Toxicology Research Division, Health and Welfare Canada, Ottawa.
Abstract:
A novel type of intoxication in Canada in 1987 was traced to consumption of cultivated mussels contaminated with the excitotoxin domoic acid. Studies carried out in rats and monkeys revealed that parenterally administered domoic acid induces in rats neuroexcitatory phenomena culminating in seizures. Monkeys respond with gagging, emesis and less clearly evident seizure activity. CNS damage consisting of dendrotoxic and gliotoxic edema and nerve cell degeneration occurs in structures of the limbic system and the retina in both species. CNS lesion distribution similarities in animals treated with domoic acid or kainic acid suggest that these excitotoxins share a common pathogenesis mediated by glutamic acid, a putative endogenous excitatory neurotransmitter.
Insights
Domoic acid, a neurotoxin from contaminated mussels, caused seizures and brain damage in rats and monkeys. This excitotoxin may share a common pathway with kainic acid, involving the neurotransmitter glutamic acid.
Area of Science:
- Neuroscience
- Toxicology
- Environmental Health
Background:
- A 1987 intoxication outbreak in Canada was linked to cultivated mussels.
- Mussel contamination was identified as originating from the excitotoxin domoic acid.
Purpose of the Study:
- To investigate the toxic effects of domoic acid in animal models.
- To understand the neurobiological mechanisms underlying domoic acid intoxication.
- To compare the effects of domoic acid with kainic acid.
Main Methods:
- Parenteral administration of domoic acid to rats and monkeys.
- Observation of neuroexcitatory phenomena, seizures, gagging, and emesis.
- Histopathological examination of central nervous system (CNS) damage, focusing on the limbic system and retina.
Main Results:
- Rats exhibited neuroexcitation and seizures; monkeys showed gagging, emesis, and less distinct seizures.
- Both species developed CNS damage, including dendrotoxic and gliotoxic edema and nerve cell degeneration in the limbic system and retina.
- Similarities in lesion distribution were observed between domoic acid and kainic acid exposure.
Conclusions:
- Domoic acid is a potent neurotoxin causing significant CNS damage.
- The pathogenesis of domoic acid toxicity may involve glutamic acid pathways, similar to kainic acid.
- Understanding these mechanisms is crucial for public health and managing neurotoxin exposure.