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迈向斑马鱼精神疾病发育模型。

Toward developmental models of psychiatric disorders in zebrafish.

机构信息

Department of Biology, College of Medicine, Biological Sciences and Psychiatry, University of Leicester Leicester, UK.

出版信息

Front Neural Circuits. 2013 Apr 26;7:79. doi: 10.3389/fncir.2013.00079. eCollection 2013.

Abstract

Psychiatric disorders are a diverse set of diseases that affect all aspects of mental function including social interaction, thinking, feeling, and mood. Although psychiatric disorders place a large economic burden on society, the drugs available to treat them are often palliative with variable efficacy and intolerable side-effects. The development of novel drugs has been hindered by a lack of knowledge about the etiology of these diseases. It is thus necessary to further investigate psychiatric disorders using a combination of human molecular genetics, gene-by-environment studies, in vitro pharmacological and biochemistry experiments, animal models, and investigation of the non-biological basis of these diseases, such as environmental effects. Many psychiatric disorders, including autism spectrum disorder, attention-deficit/hyperactivity disorder, mental retardation, and schizophrenia can be triggered by alterations to neural development. The zebrafish is a popular model for developmental biology that is increasingly used to study human disease. Recent work has extended this approach to examine psychiatric disorders as well. However, since psychiatric disorders affect complex mental functions that might be human specific, it is not possible to fully model them in fish. In this review, I will propose that the suitability of zebrafish for developmental studies, and the genetic tools available to manipulate them, provide a powerful model to study the roles of genes that are linked to psychiatric disorders during neural development. The relative speed and ease of conducting experiments in zebrafish can be used to address two areas of future research: the contribution of environmental factors to disease onset, and screening for novel therapeutic compounds.

摘要

精神障碍是一组不同的疾病,影响包括社交互动、思维、感觉和情绪在内的所有精神功能。尽管精神障碍给社会带来了巨大的经济负担,但可用的治疗药物往往疗效不一,且副作用难以忍受。新型药物的开发受到对这些疾病病因缺乏了解的阻碍。因此,有必要结合人类分子遗传学、基因-环境研究、体外药理学和生物化学实验、动物模型以及对这些疾病非生物学基础(如环境影响)的研究,进一步研究精神障碍。许多精神障碍,包括自闭症谱系障碍、注意缺陷/多动障碍、智力迟钝和精神分裂症,都可能是由于神经发育的改变而引发的。斑马鱼是一种流行的发育生物学模型,越来越多地用于研究人类疾病。最近的工作已经将这种方法扩展到研究精神障碍。然而,由于精神障碍会影响复杂的精神功能,这些功能可能是人类特有的,因此在鱼类中不可能完全模拟这些功能。在这篇综述中,我将提出,斑马鱼适合发育研究,以及可用于操纵它们的遗传工具,为研究与精神障碍相关的基因在神经发育过程中的作用提供了一个强大的模型。在斑马鱼中进行实验的相对速度和容易程度可以用于解决两个未来研究领域的问题:环境因素对疾病发作的贡献,以及筛选新型治疗化合物。

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