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Circumventricular organ origin of domoic acid-induced neuropathology and toxicology
1Department of Anatomy, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Abstract:
The neuroexcitotoxin, domoic acid, was responsible for an episode of mussel poisoning in Eastern Canada in 1987. Severe neurologic impairment and some deaths occurred. We have characterized the nature of domoate-induced neuropathology in the mouse brain. Domoic acid was administered intraperitoneally at doses of 2, 3 or 7 mg/kg to Swiss-Webster mice. Brains were examined at 0.5, 1, 24, 48 or 72 h postinjection for evidence of damage. Significant pathologic changes occurred only after the largest dose of domoic acid. Damage was confined to circumventricular organs lacking a blood-brain barrier and their environs, including the organon vasculosum of the lamina terminalis, subfornical organ, mediobasal hypothalamus and area postrema. The neural damage induced by domoic acid was evident at as early as 30 min after injection and increased by 60 min postinjection. The loci of domoic acid-induced neuropathological changes accounts for several central and peripheral effects and toxicities observed following systemic domoate treatment, these included gastroduodenal lesions, hypodipsia, analgesia, and blood pressure fluctuations.
Insights
Domoic acid, a neurotoxin from mussel poisoning, causes brain damage in mice. This damage affects specific brain regions, explaining various toxic effects observed after exposure.
Area of Science:
- Neuroscience
- Toxicology
- Pathology
Background:
- Domoic acid exposure, as seen in 1987 Canadian mussel poisoning, causes severe neurological impairment and fatalities.
- Understanding the neuropathology of domoic acid is crucial for managing its toxic effects.
Purpose of the Study:
- To characterize the neuropathological changes in the mouse brain induced by domoic acid.
- To correlate the observed brain damage with known central and peripheral toxicities of domoic acid.
Main Methods:
- Swiss-Webster mice were administered varying doses of domoic acid (2, 3, or 7 mg/kg) intraperitoneally.
- Brain tissue was examined at multiple time points (0.5 to 72 hours post-injection) for pathological alterations.
Main Results:
- Significant neuropathology was observed only at the highest domoic acid dose (7 mg/kg).
- Damage was restricted to circumventricular organs lacking a blood-brain barrier, including the organon vasculosum of the lamina terminalis, subfornical organ, mediobasal hypothalamus, and area postrema.
- Neural damage was evident as early as 30 minutes post-injection and progressed by 60 minutes.
Conclusions:
- Domoic acid selectively targets brain regions without a blood-brain barrier.
- The pattern of neuropathology explains various domoic acid toxicities, such as gastroduodenal lesions, altered thirst, pain perception, and blood pressure changes.