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Series GSE12140 Query DataSets for GSE12140
Status Public on Jul 06, 2009
Title Gene expression profiles in zebrafish brain after acute exposure to domoic acid at symptomatic and asymptomatic doses
Organism Danio rerio
Experiment type Expression profiling by array
Summary 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
 
Overall design 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.
 
Contributor(s) Beyer RP
Citation(s) 18936300
Submission date Jul 17, 2008
Last update date Jan 25, 2018
Contact name James William MacDonald
E-mail(s) jmacdon@uw.edu
Organization name University of Washington
Department Environmental and Occupational Health Sciences
Street address 4225 Roosevelt Way NE
City Seattle
State/province WA
ZIP/Postal code 98105-6099
Country USA
 
Platforms (1)
GPL1319 [Zebrafish] Affymetrix Zebrafish Genome Array
Samples (9)
GSM305891 zebrafish brain1 control
GSM305892 zebrafish brain2 control
GSM305893 zebrafish brain3 control
Relations
BioProject PRJNA113509

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE12140_RAW.tar 20.4 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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