PUBLICATION
Development and application of a brain-specific cDNA microarray for effect evaluation of neuro-active pharmaceuticals in zebrafish (Danio rerio)
- Authors
- van der Ven, K., De Wit, M., Keil, D., Moens, L., Van Leemput, K., Naudts, B., and De Coen, W.
- ID
- ZDB-PUB-050701-7
- Date
- 2005
- Source
- Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 141(4): 408-417 (Journal)
- Registered Authors
- Keywords
- Chlorpromazine; Custom microarray; Neurotoxicity; Pharmaceuticals; Toxicogenomics; Zebrafish
- MeSH Terms
-
- Animals
- Brain/drug effects*
- Brain/metabolism
- Central Nervous System Agents/pharmacology*
- Chlorpromazine/pharmacology*
- Female
- Gene Expression Regulation/drug effects
- Male
- Neurons/drug effects*
- Neurons/physiology
- Oligonucleotide Array Sequence Analysis/methods*
- Organ Specificity
- RNA/drug effects
- RNA/genetics
- Sensitivity and Specificity
- Sex Factors
- Zebrafish*
- PubMed
- 15979371 Full text @ Comp. Biochem. Physiol. B Biochem. Mol. Biol.
Citation
van der Ven, K., De Wit, M., Keil, D., Moens, L., Van Leemput, K., Naudts, B., and De Coen, W. (2005) Development and application of a brain-specific cDNA microarray for effect evaluation of neuro-active pharmaceuticals in zebrafish (Danio rerio). Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology. 141(4):408-417.
Abstract
The environmental fate and ecotoxicological effect of pharmaceuticals are poorly understood, and standardized tests to detect and evaluate their potential effects in the environment are not available. We developed a zebrafish brain-specific microarray containing 682 neurologically relevant cDNA-fragments. To investigate the applicability of this microarray for studying neurotoxic modes-of-action and impact assessment of neuro-active pharmaceuticals in zebrafish, chlorpromazine was used as a model compound. After exposure to chlorpromazine (75 mug/L) for 2, 4, 14 and 28 days or control treatment RNA was extracted from brains of males and females. Fluorescently labeled cDNA was prepared and hybridized to the custom microarray. In total, 56 genes were differentially expressed in brains of male and/or female zebrafish, of which most genes were down-regulated. A clear difference in response to chlorpromazine exposure between males and females was observed with exposure time as well as in functional classes of affected genes. The presented study is one of the first reports on molecular effects of human neuro-active pharmaceuticals in aquatic non-target organisms. This new genomic tool successfully detected gene expression effects of exposure to chlorpromazine in the brain of zebrafish. Reported gene expression effects are found to be consistent with literature data for other laboratory animals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping