Electroencephalographic, behavioral, and c-fos responses to acute domoic acid exposure

Scallet, Andrew C.; Kowalke, Pawel K; Rountree, Robert; Thorn, Brett T.; Binienda, Zbigniew

doi:10.1016/j.ntt.2003.10.004

Cited by 35 publications

(19 citation statements)

References 67 publications

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“…Rats were housed at 25°C under controlled 12-hour light/dark cycles and fed ad libitum on a standard rat diet before experimentation. All surgical and euthanasia procedures, including seizure induction and monitoring, were conducted in accordance with the regulations of the Otago University Committee on Ethics in the Care and Use of Laboratory Animals and the Guide for Care and Use of Laboratory Animals (NIH Publication 85- 23,1996).…”

Section: Animal Carementioning

confidence: 99%

“…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.…”

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confidence: 99%

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Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

Vranyac-Tramoundanas

Harrison

Sawant

et al. 2011

The American Journal of Pathology

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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.

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Section: Animal Carementioning

confidence: 99%

mentioning

confidence: 99%

Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

Vranyac-Tramoundanas

Harrison

Sawant

et al. 2011

The American Journal of Pathology

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“…These responses also parallel those observed from environmental exposures in sea lions (Gulland et al 2002). Various researchers have also reported that DA exposure causes prolonged neuroexcitation and extensive degeneration in the hippocampus as well as more rostral areas of the brain, including the septum and olfactory bulb (Peng and Ramsdell 1996; Peng et al 1994; Scallet et al 1993, 2004). DA-induced damage to hippocampal formation has been correlated with both learning (Clayton et al 1999) and memory deficits in humans and experimental animals (Nakajima and Potvin 1992; Petrie et al 1992; Sutherland et al 1990; Teitelbaum et al 1990).…”

mentioning

confidence: 99%

Domoic Acid Transfer to Milk: Evaluation of a Potential Route of Neonatal Exposure

Maucher¹,

Ramsdell²

2005

Environ Health Perspect

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Domoic acid (DA), produced by the diatom genus Pseudo-nitzschia, is a glutamate analog and a neurotoxin in humans. During diatom blooms, DA can contaminate filter-feeding organisms, such as shellfish, and can be transferred by ingestion to higher trophic levels. Several intoxication events involving both humans and various marine mammals have been attributed to DA. Affected organisms show neurological symptoms such as seizures, ataxia, headweaving, and stereotypic scratching, as well as prolonged deficits in memory and learning. Neonatal animals have been shown to be substantially more sensitive to DA than adults. However, it has not been demonstrated whether DA can be transferred to nursing young from DA-exposed mothers. This study demonstrates transfer of DA from spiked milk (0.3 and 1.0 mg/kg) to the plasma of nursing neonatal rats and an overall longer DA retention in milk than in plasma after 8 hr in exposed dams. DA was detectable in milk up to 24 hr after exposure (1.0 mg/kg) of the mothers, although the amount of DA transferred to milk after exposure was not sufficient to cause acute symptoms in neonates.

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“…The expression levels of IEGs are well correlated with seizure activity. The expression of c-fos has been used as an indicator of neuronal activity in zebrafish which is often measured by using the electroencephalography (EEG) [18], To investigate whether compounds 1 and 39 – 41 affects PTZ-induced expression of the gene c-fos , quantitative real time PCR of c-fos was performed on larval zebrafish (Figure 4C). The results indicated that the PTZ treatment (10 mM for 60 min) induced about 43-fold expression of c-fos mRNA in five dpf larval zebrafish whereas compounds 1 and 39 – 41 significantly attenuated the PTZ-induced increase in c-fos expression.…”

Section: Resultsmentioning

confidence: 99%

Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish

Long¹,

Liang²,

Wu³

et al. 2014

Marine Drugs

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High-throughput behavior-based screen in zebrafish is a powerful approach for the discovery of novel neuroactive small molecules for treatment of nervous system diseases such as epilepsy. To identify neuroactive small molecules, we first screened 36 compounds (1–36) derived from marine natural products xyloketals and marine isoprenyl phenyl ether obtained from the mangrove fungus. Compound 1 demonstrated the most potent inhibition on the locomotor activity in larval zebrafish. Compounds 37–42 were further synthesized and their potential anti-epilepsy action was then examined in a PTZ-induced epilepsy model in zebrafish. Compound 1 and compounds 39, 40 and 41 could significantly attenuate PTZ-induced locomotor hyperactivity and elevation of c-fos mRNA in larval zebrafish. Compound 40 showed the most potent inhibitory action against PTZ-induced hyperactivity. The structure-activity analysis showed that the OH group at 12-position played a critical role and the substituents at the 13-position were well tolerated in the inhibitory activity of xyloketal derivatives. Thus, these derivatives may provide some novel drug candidates for the treatment of epilepsy.

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Electroencephalographic, behavioral, and c-fos responses to acute domoic acid exposure

Cited by 35 publications

References 67 publications

Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

Domoic Acid Transfer to Milk: Evaluation of a Potential Route of Neonatal Exposure

Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish

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