PUBLICATION
Neuropharmaceuticals in the environment: mianserin-induced neuroendocrine disruption in zebrafish (Danio rerio) using cDNA microarrays
- Authors
- van der Ven, K., Keil, D., Moens, L.N., Van Leemput, K., van Remortel, P., and De Coen, W.M.
- ID
- ZDB-PUB-061020-21
- Date
- 2006
- Source
- Environmental toxicology and chemistry 25(10): 2645-2652 (Journal)
- Registered Authors
- Keywords
- Pharmaceuticals, Zebrafish, Toxicogenomics, Microarray, Mianserin
- MeSH Terms
-
- Animals
- Base Sequence
- Brain/drug effects*
- DNA Primers
- DNA, Complementary
- Endocrine Disruptors/toxicity*
- Gene Expression/drug effects
- Mianserin/toxicity*
- Oligonucleotide Array Sequence Analysis
- Polymerase Chain Reaction
- Reproduction/drug effects
- Water Pollutants, Chemical/toxicity*
- Zebrafish
- PubMed
- 17022405 Full text @ Environ. Toxicol. Chem.
Citation
van der Ven, K., Keil, D., Moens, L.N., Van Leemput, K., van Remortel, P., and De Coen, W.M. (2006) Neuropharmaceuticals in the environment: mianserin-induced neuroendocrine disruption in zebrafish (Danio rerio) using cDNA microarrays. Environmental toxicology and chemistry. 25(10):2645-2652.
Abstract
Because of their environmental occurrence and high biological activity, human pharmaceuticals have received increasing attention from environmental and health agencies. A major bottleneck in their risk assessment is the lack of relevant and specific effect data. We developed an approach using gene expression analysis in quantifying adverse effects of neuroendocrine pharmaceuticals in the environment. We studied effects of mianserin on zebrafish (Danio rerio) gene expression using a brain-specific, custom microarray, with real-time polymerase chain reaction as confirmation. After exposure (0, 25, and 250 microg/L) for 2, 4, and 14 d, RNA was extracted from brain tissue and used for microarray hybridization. In parallel, we investigated the impact of exposure on egg production, fertilization, and hatching. After 2 d of exposure, microarray analysis showed a clear effect of mianserin on important neuroendocrine-related genes (e.g., aromatase and estrogen receptor), indicating that antidepressants can modulate neuroendocrine processes. This initial neuroendocrine effect was followed by a "late gene expression effect" on neuronal plasticity, supporting the current concept regarding the mode of action for antidepressants in mammals. Clear adverse effects on egg viability were seen after 14 d of exposure at the highest concentration tested. Based on the specific molecular impact and the effects on reproduction, we conclude that further investigation of the adverse effects on the brain-liver-gonad axis is needed for a correct ecological risk assessment of antidepressants.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping