R3 AM Ecotoxicogenomics of Emerging Chemical Issues
Thursday, 17 November 2005: 8:00 AM - 11:40 AM in Ballroom 3

(VAN-1117-804539) Toxicogenomic analysis of zebrafish brain as a potential new tool for effect evaluation of neuropharmaceuticals.

van der Ven, K¹, Keil, D¹, De Wit, M¹, Moens, L¹, Soetaert, A¹, Van Leemput, K², Naudts, B², Blust, R¹, De Coen, W¹, ¹ Laboratory of Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Antwerp, Antwerp, Belgium² Intelligent Systems Laboratory, University of Antwerp

ABSTRACT- Due to their environmental occurrence human pharmaceuticals have received increasing attention from environmental and health agencies across the European Union and in North America. Several studies have already identified a variety of drugs in waste-, surface-, and drinking water, but very little is currently known about their effects on non-target organisms. In order to evaluate this environmental impact correctly, short term assays need to be developed which assess the specific modes of action of these highly potent molecules. We have developed a custom-microarray containing a selected brain-specific zebrafish gene-set representing genes of specific relevance to investigate toxicological impact on important neuro-endocrine pathways. To test the applicability of this array for studying effects of exposure to neuro-active pharmaceuticals in teleosts, differential gene expression was analysed after water-exposure of zebrafish to different concentrations of chlorpromazine and mianserin at different time-intervals. Gene expression analysis indicated a clear male versus female difference in response to chlorpromazine. In female fish several genes related to cell structure and cytoskeleton were differentially expressed. The observed effects of exposure to mianserin on gene expression suggested crucial genes involved in important neuro-endocrine pathways to be affected (e.g. aromatase, estrogen receptor). In parallel with gene expression analysis we investigated the ecological relevance of these signals by assessing the effect of exposure on reproductive endpoints. Clear adverse effects on larvae survival were seen after exposure to mianserin. Data will also be presented of effects on gene expression in the brain of zebrafish in parallel with reproductive and behavioral effects after exposure to a mixture of neuropharmaceuticals at environmental relealistic concentrations. The integration of higher level effect parameters with the DNA microarray-based study of gene expression changes in the brain of zebrafish could create, potentially, a powerful technique for risk prioritizing and environmental research of neuropharmaceuticals.

Key words: toxicogenomics, neuropharmaceutical, zebrafish, microarray