Hill Adrian, Howard C Vyvyan, Strahle Uwe, Cossins Andrew
Laboratory for Environmental Gene Regulation, School of Biological Sciences, Biosciences Building, University of Liverpool, Crown Street, Liverpool Merseyside L69 7ZB, United Kingdom.
Toxicol Sci. 2003 Dec;76(2):392-9. doi: 10.1093/toxsci/kfg241. Epub 2003 Nov 4.
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.
持久性生态毒素，如二恶英和多氯联苯，被认为是工业世界中对公众和生态健康构成最大威胁的因素之一。这些化合物会导致一系列宏观畸形，尤其是在脊椎动物发育过程中对颅面器官和心血管系统造成影响。然而，对于微观影响，特别是对敏感的生命早期阶段或发育性神经毒性的分子基础，人们了解甚少。我们利用斑马鱼（Danio rerio），探索了生命早期接触环境相关浓度二恶英所导致的神经缺陷。我们使用定量立体学技术表明，2,3,7,8-四氯二苯并对二恶英（TCDD）显著降低了胚胎脑发育能力，导致168小时龄幼虫脑中总神经元数量减少30%。利用表达绿色荧光蛋白的转基因斑马鱼品系，我们将此与关键发育调控基因即神经生成素和音猬因子的表达降低联系起来。这种神经元发育的破坏为理解这些化合物的神经毒性作用提供了基础。
