Domoic acid: Neurobehavioral consequences of exposure to a prevalent marine biotoxin

Abstract

Domoic acid (DA), the cause of Amnesic Shellfish Poisoning, is a naturally occurring marine biotoxin that is usually produced by the microscopic algae Pseudo-nitzschia. As is the case for other types of toxic algae, Pseudo-nitzschia outbreaks are becoming more frequent. Acute high-dose symptomology in humans includes vomiting, cramping, coma and death as well as neurological effects such as hallucinations, confusion and memory loss. Experimental studies and medical reports have collectively shown that DA exposure primarily affects the hippocampal regions of the brain and is associated with seizures and the disruption of cognitive processes. The neurobehavioral signature of DA is unique in that it includes transient and permanent changes in memory function that resemble human antegrade amnesia. Experimental studies with adult nonhuman primates have established that DA is a dose-dependent emetic that produces clinical and neuropathological changes consistent with excitotoxicity. Behavioral evaluations of treated rodents have shown that hyperactivity and stereotypical scratching are the first functional markers of toxicity. Mid-dose treatment is associated with memory impairment and behavioral hyperreactivity, suggesting changes in arousal and/or emotionality. At higher doses, DA treatment results in frank neurotoxicity that is characterized by seizures, status epilepticus and death in treated animals. The route of DA exposure is important and influences the severity of effects; intraperitoneal and intravenous treatments produce classic signs of poisoning at significantly lower doses than oral exposure. While developmental studies are few, DA readily crosses the placenta and enters the fetal brain. Domoic acid is not associated with congenital dysmorphia but is linked to persistent changes in motor behavior and cognition in exposed offspring. Comparative research suggests that functional losses associated with DA can be persistent and injuries to the CNS can be progressive. Long-term studies will be necessary to accurately track the expression of DA-related injury, in health and behavior, over the life-span.

Adverse Outcome Pathway on binding of agonists to ionotropic glutamate receptors in adult brain leading to excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment

“…In humans, the hallmark of DomA-induced neurotoxicity is the rather dramatic disruption of memory processing. Clinical evaluation of 14 adult human subjects poisoned by DomA (after the outbreak in Canada) revealed that the majority of them (12/14) had severe antegrade memory deficits with relative preservation of higher cortical functions, since the patients were unable to remember events that occurred after DomA intoxication and had difficulty recalling new information (reviewed in Grant et al, 2010).…”

“…In a separate clinical report of one case, a patient that received treatment at the hospital for DomA poisoning showed memory impairment which was resolved after three weeks (reviewed in Grant et al, 2010). Other symptoms of the syndrome include nausea, vomiting, abdominal cramps, diarrhoea, headache, unstable blood pressure, cardiac arrhythmias and neurological dysfunction, including coma and seizures (reviewed in Grant et al, 2010).…”

SEASONAL AND SPATIAL PATTERNS OF TOXIGENIC SPECIES OF Dinophysis AND Pseudo-nitzschia IN A SUBTROPICAL BRAZILIAN ESTUARY

“…In addition to the DSP-causing toxins, domoic acid (DA) -the main toxin which causes ASP outbreaks, produced by several species of the diatom Pseudo-nitzschia (JEFFERY et al, 2004;GRANT et al, 2010) -has also been recorded in South Brazil (PROENÇA;MAFRA Jr., 2005). Domoic acid, which is responsible for massive mortalities of birds and marine mammals following the ingestion of contaminated fish (BELTRÀN et al, 1997;LEFEBVRE et al, 1999), can also intoxicate humans through the consumption of bivalve mollusks that accumulate the toxin in their tissues, mainly in the hepatopancreas and viscera (PERL et al, 1990;GRANT et al, 2010;MAFRA et al, 2010).…”

“…Domoic acid, which is responsible for massive mortalities of birds and marine mammals following the ingestion of contaminated fish (BELTRÀN et al, 1997;LEFEBVRE et al, 1999), can also intoxicate humans through the consumption of bivalve mollusks that accumulate the toxin in their tissues, mainly in the hepatopancreas and viscera (PERL et al, 1990;GRANT et al, 2010;MAFRA et al, 2010). Although, only in special episodes, when a large number of Pseudo-nitzschia spp.…”

“…Although, only in special episodes, when a large number of Pseudo-nitzschia spp. cells containing high DA concentrations occur in coastal waters, are bivalve mollusks capable of accumulating sufficient toxin to affect humans, causing gastrointestinal and neurological symptoms (JEFFERY et al, 2004;GRANT et al, 2010). During the major 1987 Pseudonitzschia multiseries bloom on Prince Edward Island, Canada, more than 100 people were hospitalized, and four patients died (PERL et al, 1990).…”