Neurodevelopmental Defects in Zebrafish (Danio rerio) at Environmentally Relevant Dioxin (TCDD) Concentrations

• Published in: Toxicological Sciences 2003-12, Vol.76 (2), p.392-399
• Main Authors: Hill, Adrian, Howard, C. Vyvyan, Strahle, Uwe, Cossins, Andrew
• Format: Article
• Language: English
• Subjects: Agnatha. Pisces; Animal, plant and microbial ecology; Animals; Animals, Genetically Modified; Apoptosis - drug effects; Applied ecology; Basic Helix-Loop-Helix Transcription Factors; Biological and medical sciences; Brain - abnormalities; Brain - drug effects; Danio rerio; Dose-Response Relationship, Drug; Ecotoxicology, biological effects of pollution; Effects of pollution and side effects of pesticides on vertebrates; embryo; Embryo, Nonmammalian - abnormalities; Embryo, Nonmammalian - drug effects; Embryo, Nonmammalian - metabolism; Environmental Pollutants - toxicity; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental - drug effects; Hedgehog Proteins; In Situ Hybridization; Life Sciences; Nerve Tissue Proteins - genetics; neurogenin; neurotoxicity; Polychlorinated Dibenzodioxins - toxicity; sonic hedgehog; TCDD; Toxicology; Trans-Activators - genetics; Transcription Factors - genetics; zebrafish; Zebrafish - embryology; Zebrafish - genetics; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 1096-6080; 1096-0929; 1096-0929; 1096-6099
• DOI: 10.1093/toxsci/kfg241

Persistent ecotoxicants, such as dioxin and PCBs, are thought to pose one of the greatest threats to public and ecological health in the industrial world. These compounds cause a range of macroscopic malformations, particularly to the craniofacial apparatus and cardiovascular system during vertebrate development. However, little is known about microscopic effects, especially on the sensitive early life stages or on the molecular basis of developmental neurotoxicity. Using zebrafish (Danio rerio), we have explored neurological deficits caused by early-life exposure to environmentally relevant concentrations of dioxin. We show, using a quantitative stereological technique, that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) substantially reduces the capacity for embryonic brain development, causing a 30% reduction in total neuronal number in the 168-h larval brain. Using transgenic GFP-expressing zebrafish lines, we link this to decreased expression of key developmentally regulated genes, namely neurogenin and sonic hedgehog. This disruption of neuronal development provides the basis for understanding the neurotoxic effects of these compounds.