Transcriptomics

Dataset Information

4

Gene expression profiles in zebrafish brain after acute exposure to domoic acid at symptomatic and asymptomatic doses


ABSTRACT: Domoic acid (DA) is a neuroexcitatory amino acid that is naturally produced by some marine diatom species of the genus Pseudo-nitzschia. Ingestion of DA-contaminated seafood by humans results in a severe neurotoxic disease known as amnesic shellfish poisoning (ASP). Clinical signs of ASP include seizures and neuronal damage from activation of AMPA and kainate receptors. However, the impacts of DA exposure at levels below those known to induce outward signs of neurobehavioral exicitotoxicity have not been well characterized. To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. Transcriptional profiles were suggestive of neuronal apoptosis following an overwhelming of protective adaptive pathways. Further, potential molecular biomarkers of neuropathic injury, including Nrdg4, were identified and may be relevant to DA exposure levels below that causing neurobehavioral injury. Our results validate zebrafish as a vertebrate model to study mechanisms of DA neurotoxicity and provide a basis for identifying pathways of DA-induced injury as well as biomarkers of asymptomatic and symptomatic DA exposure levels. Keywords: neurotoxic disease To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. All animal studies were carried out under approved IACUC protocols at the University of Washington.

ORGANISM(S): Danio rerio  

SUBMITTER: Richard Beyer   Richard P Beyer 

PROVIDER: E-GEOD-12140 | ArrayExpress | 2009-07-06

SECONDARY ACCESSION(S): GSE12140PRJNA113509

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications

Gene expression profiles in zebrafish brain after acute exposure to domoic acid at symptomatic and asymptomatic doses.

Lefebvre Kathi A KA   Tilton Susan C SC   Bammler Theo K TK   Beyer Richard P RP   Srinouanprachan Sengkeo S   Stapleton Patricia L PL   Farin Federico M FM   Gallagher Evan P EP  

Toxicological sciences : an official journal of the Society of Toxicology 20081020 1


Domoic acid (DA) is a neuroexcitatory amino acid that is naturally produced by some marine diatom species of the genus Pseudo-nitzschia. Ingestion of DA-contaminated seafood by humans results in a severe neurotoxic disease known as amnesic shellfish poisoning (ASP). Clinical signs of ASP include seizures and neuronal damage from activation of ionotropic glutamate receptors. However, the impacts of DA exposure at levels below those known to induce outward signs of neurobehavioral exicitotoxicity  ...[more]

Similar Datasets

2009-07-06 | GSE12140 | GEO
2013-01-03 | E-GEOD-34716 | ArrayExpress
2006-02-10 | E-MEXP-268 | ArrayExpress
2012-12-01 | E-GEOD-33373 | ArrayExpress
2012-05-14 | E-GEOD-37970 | ArrayExpress
2012-05-31 | E-GEOD-22634 | ArrayExpress
2009-08-07 | E-GEOD-12214 | ArrayExpress
2012-09-06 | E-GEOD-31712 | ArrayExpress
2010-06-05 | E-GEOD-18861 | ArrayExpress
2013-09-06 | E-GEOD-50634 | ArrayExpress