Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Nicotine Tob Res. 2011 May;13(5):301-12. doi: 10.1093/ntr/ntr010. Epub 2011 Mar 8.
Zebrafish are emerging as a powerful animal model for studying the molecular and physiological effects of nicotine exposure. The zebrafish have many advantageous physical characteristics, including small size, high fecundity rates, and externally developing transparent embryos. When combined with a battery of molecular-genetic tools and behavioral assays, these attributes enable studies to be conducted that are not practical using traditional animal models.
We reviewed the literature on the application of the zebrafish model as a preclinical model to study the biological effects of nicotine exposure.
The identified studies used zebrafish to examine the effects of nicotine exposure on early development, addiction, anxiety, and learning. The methods used included green fluorescent protein-labeled proteins to track in vivo nicotine-altered neuron development, nicotine-conditioned place preference, and locomotive sensitization linked with high-throughput molecular and genetic screens and behavioral models of learning and stress response to nicotine. Data are presented on the complete homology of all known human neural nicotinic acetylcholine receptors in zebrafish and on the biological similarity of human and zebrafish dopaminergic signaling.
Tobacco dependence remains a major health problem worldwide. Further understanding of the molecular effects of nicotine exposure and genetic contributions to dependence may lead to improvement in patient treatment strategies. While there are limitations to the use of zebrafish as a preclinical model, it should provide a valuable tool to complement existing model systems. The reviewed studies demonstrate the enormous opportunity zebrafish have to advance the science of nicotine and tobacco research.
斑马鱼正逐渐成为研究尼古丁暴露的分子和生理效应的强大动物模型。斑马鱼具有许多有利的物理特性,包括体型小、高繁殖率和体外发育的透明胚胎。当与一系列分子遗传工具和行为分析结合使用时,这些特性使得一些使用传统动物模型无法进行的研究成为可能。
我们回顾了关于将斑马鱼模型作为临床前模型应用于研究尼古丁暴露的生物学效应的文献。
已确定的研究使用斑马鱼来研究尼古丁暴露对早期发育、成瘾、焦虑和学习的影响。所使用的方法包括用绿色荧光蛋白标记蛋白来追踪体内尼古丁改变的神经元发育、尼古丁条件性位置偏好以及与高通量分子和遗传筛选以及学习和应激反应的行为模型相关的运动敏化。数据显示,所有已知的人类神经烟碱型乙酰胆碱受体在斑马鱼中具有完全同源性,并且人类和斑马鱼多巴胺信号传递具有生物学相似性。
全球范围内,烟草依赖仍然是一个主要的健康问题。进一步了解尼古丁暴露的分子效应和遗传因素对依赖性的影响,可能会改善患者的治疗策略。虽然使用斑马鱼作为临床前模型存在局限性,但它应该为补充现有模型系统提供有价值的工具。综述中的研究表明,斑马鱼在推进尼古丁和烟草研究科学方面具有巨大的机会。