Disease relevance of C13732

• In late 1987 there was an outbreak in Canada of gastrointestinal and neurologic symptoms after the consumption of mussels found to be contaminated with domoic acid, which is structurally related to the excitatory neurotransmitter glutamate [1].
• An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid [2].
• Such findings reveal that monitoring of mussel toxicity alone does not necessarily provide adequate warning of DA entering the food web at levels sufficient to harm marine wildlife and perhaps humans [3].
• Domoic acid (DA), a potent neurotoxin, administered intravenously (0.75 mg/kg body weight) in adult rats evoked seizures accompanied by nerve cell damage in the present study [4].
• After intraperitoneal (i.p.) administration of domoic acid (6 mg/kg), electrographic spikes appeared at increasing frequency, progressing to high-amplitude (0.1-0.8 mV) continuous seizure activity (status epilepticus) [5].

Psychiatry related information on C13732

• We conclude that intoxication with domoic acid causes a novel and distinct clinicopathologic syndrome characterized initially by widespread neurologic dysfunction and then by chronic residual memory deficits and motor neuronopathy or axonopathy [1].
• This study investigated the role of cellular antioxidant defense mechanisms in modulating the neurotoxicity of domoic acid (DomA), by using cerebellar granule neurons (CGNs) from mice lacking the modifier subunit of glutamate-cysteine ligase (Gclm) [6].
• In approximately 60% of rats to which it was administered, domoic acid caused stereotyped behavior within 60 min, followed by convulsions within 2-3 h [7].
• Animals, such as pelicans, cormorants, loons, grebes, sea otters, dolphins, and sea lions, which consume seafood contaminated with domoic acid, suffer disorientation and often death [8].
• Prenatal domoic acid exposure caused a dose-related increase in response latency in the second spontaneous alternation test [9].

High impact information on C13732

• This bloom was associated with production of domoic acid (DA), a neurotoxin that was also detected in planktivorous fish, including the northern anchovy (Engraulis mordax), and in sea lion body fluids [3].
• Toxicology of mussels contaminated by neuroexcitant domoic acid [10].
• We describe the development of temporal lobe epilepsy in an 84-year-old man who had suffered domoic acid intoxication [11].
• Temporal lobe epilepsy caused by domoic acid intoxication: evidence for glutamate receptor-mediated excitotoxicity in humans [11].
• Domoic acid (0.6 mg/kg) was injected intravenously through the caudal vein in pregnant female mice on the 13th day of gestation and EEG was monitored in the developing progeny during postnatal days 10-30 [12].

Chemical compound and disease context of C13732

• Comparative behavioural toxicity of domoic acid and kainic acid in neonatal rats [13].
• Domoic acid-induced myocarditis appears to progress to DCM, and depletion of myocardial L-carnitine may play a key role in this pathogenesis [14].
• This reduced toxicity is consistent with a lack of absorption from the gastro-intestinal tract: faecal excretion accounted for 102 +/- 17% and 98 +/- 12% (mean +/- SE) of the domoic acid administered to mice and rats, respectively [15].

Biological context of C13732

• These data, to our knowledge, are the first detailed descriptions of the cell death mechanisms following domoic acid treatment of neurons [16].
• 3. Kainic acid and domoic acid both appeared to displace [3H]-kainic acid from a single binding site with equilibrium binding constants of KD = 19.4 nM and Ki = 14.5 nM respectively [17].
• Phosphate energy metabolism during domoic acid-induced seizures [5].
• Adult female mice were subjected intraperitoneally to domoic acid at the lethal dose 50, killed and dissected at 30, 60 and 240 min post-injection [18].
• Acute phase gene expression in mice exposed to the marine neurotoxin domoic acid [18].

Anatomical context of C13732

• Neuronal degeneration followed by detection of nitric oxide (NO)-producing neurons of the hippocampus was investigated at 4 h, 16 h, 24 h, 2 days, 5 days, and 14 days after administration of domoic acid (DA), in the present study [19].
• Subcellular fractionation and lesioning experiments using the excitotoxin domoic acid indicated that the alpha-amino-3-hydroxyl-5-methyl-isoxazole-4-propionate receptor subunits were associated with postsynaptic membranes [20].
• Results indicate that the primary health effects associated with domoic acid toxicity can be averted in populations of concern and for others consuming crabs or clams less frequently (or in lesser quantity) if domoic acid contaminant concentration does not exceed 30 mg/kg in the hepatopancreas and viscera of dungeness crabs or 20 mg/kg in clams [21].
• 3. In the isolated dorsal root fibre, domoic acid caused the most significant depolarization [22].
• Induction of inducible nitric oxide synthase expression in activated microglia following domoic acid (DA)-induced neurotoxicity in the rat hippocampus [23].

Associations of C13732 with other chemical compounds

• Neurotoxicity of domoic Acid in cerebellar granule neurons in a genetic model of glutathione deficiency [6].
• Neuronal activities were blocked by microinjections of the glutamate antagonist MK-801 and were destroyed by the neurotoxins kainic acid and domoic acid [24].
• Protective role of melatonin in domoic acid-induced neuronal damage in the hippocampus of adult rats [25].
• Domoic acid (DA) is a neurotoxic amino acid that is responsible for the human toxic syndrome, amnesic shellfish poisoning (ASP) [26].
• In conclusion, based on results with a microdialysis technique, we suggest that domoic acid may act through AMPA/kainate receptors in striatum [27].

Gene context of C13732

• Distribution of NADPH-diaphorase and expression of nNOS, N-methyl-D-aspartate receptor (NMDAR1) and non-NMDA glutamate receptor (GlutR2) genes in the neurons of the hippocampus after domoic acid-induced lesions in adult rats [19].
• Using DA-3 antibody, an indirect competitive enzyme immunoassay (idc-EIA) was developed for measurement of domoic acid [28].
• For production of monoclonal antibodies against domoic acid, a causative agent of amnesic shellfish poisoning, three immunogens, domoic acid conjugated with bovine serum albumin (BSA), ovalbumin (OVA) and human gamma globulin (HGG), were prepared [28].
• Animals pretreated with diazepam (5 mg/kg, ip) tolerated intraventricular dose of domoic acid 0.4 microgram, but showed a loss of pyramidal neurons mainly in the CA3, CA4, and a part of CA1 areas of the dorsal hippocampus [29].
• Furthermore, though less potent than LPS, a 4-hour treatment with domoic acid (1 mM) yielded a 757% (p < 0.01) increase in MMP-9 release, but had no effect on MMP-2 [30].

Analytical, diagnostic and therapeutic context of C13732

• Intrauterine domoic acid-exposed (IUD) mice had significantly reduced seizure thresholds to an additional dose of domoic acid, given postnatally [12].
• The purification was carried out in two steps: ion exchange chromatography using DEAE-Sepharose CL-6B and affinity chromatography with domoic acid immobilized on Sepharose 4B [31].
• The amount of domoic acid (DA) present in the growth media and in the homogenized cells has been determined by HPLC [32].
• Methods for the analysis of domoic acid (DA) based upon capillary electrophoresis (CE) combined with UV absorbance detection were investigated [33].
• Preparation and characterization of domoic acid-protein conjugates using small amount of toxin in a reversed micellar medium: application in a competitive enzyme-linked immunosorbent assay [34].

References