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Neuropharmaceuticals in the environment: Mianserin‐induced neuroendocrine disruption in zebrafish ( Danio rerio ) using cDNA microarrays
Author(s) -
van der Ven Karlijn,
Keil Dorien,
Moens Lotte N.,
van Leemput Koen,
van Remortel Piet,
de Coen Wim M.
Publication year - 2006
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1897/05-495r.1
Subject(s) - danio , zebrafish , biology , microarray , microarray analysis techniques , aromatase , gene expression , dna microarray , gene expression profiling , pharmacology , gene , genetics , cancer , breast cancer
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 μg/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.