Ethanol effects on the developing zebrafish: neurobehavior and skeletal morphogenesis
Ethanol effects on the developing zebrafish: neurobehavior and skeletal morphogenesis
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DOI：
10.1016/j.ntt.2004.06.016
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发表时间：
2004-11-01
影响因子：
2.9
通讯作者：
Williams, FE
中科院分区：
文献类型：
--
作者：
Carvan, MJ;Loucks, E;Williams, FE
在发育过程中接触乙醇会导致一系列先天性异常，导致产前和产后发育不良、中枢神经系统 (CNS) 缺陷以及许多导致心血管系统、面部结构和四肢缺陷的模式缺陷。尽管乙醇是出生缺陷的更常见的非遗传原因之一，但乙醇发挥其发育毒性的细胞、生化和分子机制以及影响发育乙醇暴露敏感性的基因尚未被发现。斑马鱼经历了与其他脊椎动物胚胎（包括人类）大致相同的模式和形态发生，这些是独特的，无法在无脊椎动物中进行研究。斑马鱼的发育过程会以剂量依赖性方式受到乙醇暴露的影响，导致学习和记忆缺陷、中枢神经系统细胞死亡、骨骼畸形发生以及惊吓反射反应的改变。有趣的是，乙醇对学习和行为终点的显着影响发生在远低于诱导中枢神经系统细胞死亡的浓度下。这项工作为鉴定与脊椎动物发育酒精毒性有关的基因和途径奠定了基础，从而对人类胎儿酒精障碍有更完整的机制理解。 (C) 2004 Elsevier Inc. 保留所有权利。
Exposure to ethanol during development can lead to a constellation of congenital anomalies, resulting in prenatal and postnatal failure to thrive, central nervous system (CNS) deficits, and a number of patterning defects that lead to defects in the cardiovascular system, facial structures, and limbs. The cellular, biochemical, and molecular mechanisms by which ethanol exerts its developmental toxicity and the genes that influence sensitivity to developmental ethanol exposure have yet to be discovered, despite being one of the more common nongenetic causes of birth defects. The zebrafish undergoes much the same patterning and morphogenesis as other vertebrate embryos do-including humans-that are distinct and cannot be studied in invertebrates. Developmental processes in zebrafish are affected by ethanol exposure in a dose-dependent manner, resulting in learning and memory deficits, cell death in the CNS, skeletal dysmorphogenesis, and alterations in startle reflex responses. Interestingly, significant ethanol effects on learning and behavioral endpoints occurred at concentrations well below those that induced cell death in the CNS. This work provides the foundation for identifying genes and pathways involved in developmental alcohol toxicity in vertebrates, leading to a more complete mechanistic understanding of fetal alcohol disorders in humans. (C) 2004 Elsevier Inc. All rights reserved.