Comparative behavioural toxicity of domoic acid and kainic acid in neonatal rats

Doucette, Tracy A.; Strain, S. M.; Allen, Gary V.; Ryan, Catherine L.; Tasker, R. Andrew

doi:10.1016/s0892-0362(00)00110-0

Cited by 65 publications

(47 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Given the recognized neuroexcitatory effects of DA via glutamate receptors, the observed behavioral dysfunction is perhaps not surprising, however, specific mechanisms for these and other effects, particularly including morphological abnormalities, have not been clarified. That said, observed behavioral effects of DA in zebrafish embryos parallel those reported for rodent models (Xi et al, 1997;Doucette et al, 2000) that specifically indicate structural changes in the hippocampus of DA-exposed neonatal rats (Dakshinamurti et al, 1993).…”

Section: Freshwater Fish As Models For Developmental Toxins From Marisupporting

confidence: 65%

The zebrafish (Danio rerio) embryo as a model system for identification and characterization of developmental toxins from marine and freshwater microalgae

Berry

Gantar

Gibbs

et al. 2007

Comparative Biochemistry and Physiology Part C: Toxicology &

109

View full text Add to dashboard Cite

The zebrafish (Danio rerio) embryo has emerged as an important model of vertebrate development. As such, this model system is finding utility in the investigation of toxic agents that inhibit, or otherwise interfere with, developmental processes (i.e. developmental toxins), including compounds that have potential relevance to both human and environmental health, as well as biomedicine. Recently, this system has been applied increasingly to the study of microbial toxins, and more specifically, as an aquatic animal model, has been employed to investigate toxins from marine and freshwater microalgae, including those classified among the so-called "harmful algal blooms" (HABs). We have developed this system for identification and characterization of toxins from cyanobacteria (i.e. "blue-green algae") isolated from the Florida Everglades and other freshwater sources in South and Central Florida. Here we review the use of this system as it has been applied generally to the investigation of toxins from marine and freshwater microalgae, and illustrate this utility as we have applied it to the detection, bioassay-guided fractionation and subsequent characterization of developmental toxins from freshwater cyanobacteria.

show abstract

Section: Freshwater Fish As Models For Developmental Toxins From Marisupporting

confidence: 65%

The zebrafish (Danio rerio) embryo as a model system for identification and characterization of developmental toxins from marine and freshwater microalgae

Berry

Gantar

Gibbs

et al. 2007

Comparative Biochemistry and Physiology Part C: Toxicology &

109

View full text Add to dashboard Cite

show abstract

“…1,5,6,8,21,22 Of direct relevance to development of our hypothesis were indications that systemic dosing with domoic and kainic acids provoke the formation of epileptiform activity originating primarily from the hippocampus. 49 Using intrahippocampal dosed animals, Sawant and colleagues 13 from our research group used electrocorticography to show that DOM-induced epileptiform discharges spread rapidly to surrounding extralimbic regions.…”

Section: Discussionmentioning

confidence: 89%

“…[15][16][17][18][19][20] DOM has been shown to be 8 to 10 times more potent than kainic acid in rodents, producing a similar reproducible pattern of behavioral toxicity culminating in seizures. 8,21,22 Studies conducted in rats, mice, and cynomolgus monkeys have shown a consistent pattern of DOM-induced damage to the hippocampal pyramidal neurons, as well as to the thalamic, amygdalar, entorhinal, cortical, and septal neurons after DOM administration (0.22 to 4.4 mg/kg i.p.). 9,[23][24][25] With the use of electroencephalographic recordings, these studies showed that the hippocampal damage resulted in generalized epileptiform activity.…”

mentioning

confidence: 93%

Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

Vranyac-Tramoundanas

Harrison

Sawant

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Exposure to the excitotoxin domoic acid (DOM) has been shown to produce cardiac lesions in both clinical and animal studies. We have previously shown that DOM failed to directly affect cardiomyocyte viability and energetics, but the development of this cardiomyopathy has remained unexplained. The present study compared effects of high-level seizure induction obtained by intraperitoneal (2 mg/kg) or intrahippocampal (100 pmol) bolus administration of DOM on development of cardiac pathologies in a rat model. Assessment of cardiac pressure derivatives and coronary flow rates revealed a significant time-dependent decrease in combined left ventricular (LV) systolic and diastolic function at 1, 3, 7, and 14 days after intraperitoneal administration and at 7 and 14 days after intrahippocampal DOM administration. LV dysfunction was matched by a similar time-dependent decrease in mitochondrial respiratory control, associated with increased proton leakage, and in mitochondrial enzyme activities. Microscopic examination of the LV midplane revealed evidence of progressive multifocal ischemic damage within the subendocardial, septal, and papillary regions. Lesions ranged from reversible early damage (vacuolization) to hypercontracture and inflammatory necrosis progressing to fibrotic scarring. Plasma proinflammatory IL-1␣, IL-1␤, and TNF-␣ cytokine levels were also increased from 3 days after seizure induction. The observed cardiomyopathies did not differ between intraperitoneal and intrahippocampal groups, providing strong evidence that cardiac damage after DOM exposure is a consequence of a seizure-evoked autonomic response.

show abstract

“…On PND 8 to 14, each rat received a daily injection (subcutaneous; 10 ml/kg) of either saline or 20 μg/kg (0.020 mg/kg) DOM. This dose of DOM and this administration protocol has been shown to produce no overt signs of behavioral toxicity in neonatal rats [38] but to be centrally active [39]. Injections were given during the light phase of the light/dark cycle and were given at approximately the same time each day.…”

Section: Experimental Animals and Injection Protocolmentioning

confidence: 99%

Progressive changes in hippocampal cytoarchitecture in a neurodevelopmental rat model of epilepsy: implications for understanding presymptomatic epileptogenesis, predictive diagnosis, and targeted treatments

et al. 2017

View full text Add to dashboard Cite

Epilepsies affect about 4% of the population and are frequently characterized by a prolonged Bsilent^period before the onset of spontaneous seizures. Most current animal models of epilepsy either involve acute seizure induction or kindling protocols that induce repetitive seizures. We have developed a rat model of epilepsy that is characterized by a slowly progressing series of behavioral abnormalities prior to the onset of behavioral seizures. In the current study, we further describe an accompanying progression of cytoarchitectural changes in the hippocampal formation. Groups of male and female SD rats received serial injections of a low dose of domoic acid (0.020 mg/kg) (or vehicle) throughout the second week of life. Postmortem hippocampal tissue was obtained on postnatal days 29, 64, and 90 and processed for glial fibrillary acidic protein (GFAP), NeuN, and calbindin expression. The data revealed no significant changes on postnatal day (PND) 29 but a significant increase in hilar NeuN-positive cells in some regions on PND 64 and 90 that were identified as ectopic granule cells. Further, an increase in GFAP positive cell counts and evidence of reactive astrogliosis was found on PND 90 but not at earlier time points. We conclude that changes in cellular expression, possibly due to on-going non-convulsive seizures, develop slowly in this model and may contribute to progressive brain dysfunction that culminates in a seizure-prone phenotype.

show abstract

Comparative behavioural toxicity of domoic acid and kainic acid in neonatal rats

Cited by 65 publications

References 36 publications

The zebrafish (Danio rerio) embryo as a model system for identification and characterization of developmental toxins from marine and freshwater microalgae

The zebrafish (Danio rerio) embryo as a model system for identification and characterization of developmental toxins from marine and freshwater microalgae

Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

Progressive changes in hippocampal cytoarchitecture in a neurodevelopmental rat model of epilepsy: implications for understanding presymptomatic epileptogenesis, predictive diagnosis, and targeted treatments

Contact Info

Product

Resources

About