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自闭症谱系障碍啮齿动物模型的治疗方法

Treatment Approaches in Rodent Models for Autism Spectrum Disorder.

作者信息

Pietropaolo Susanna, Crusio Wim E, D'amato Francesca R

机构信息

INCIA, University of Bordeaux, Bat B2, Allée Geoffroy St. Hilaire, CS 50023, 33615, Pessac Cedex, France.

INCIA, UMR 5287, CNRS, Bat B2, Allée Geoffroy St. Hilaire, CS 50023, 33615, Pessac Cedex, France.

出版信息

Curr Top Behav Neurosci. 2017;30:325-340. doi: 10.1007/7854_2015_433.

Abstract

Recent years have seen an impressive amount of research devoted to the developing of therapies to treat autism spectrum disorder (ASD). This work has been largely based on rodent models, employing a multitude of genetic and environmental manipulations. Unfortunately, the task of identifying suitable treatments for ASD is extremely challenging, due to a variety of problems specific to the research in this field. Here, we first discuss these problems, including (I) the presence of a large variety of rodent models (often without universal consensus on their validity), (II) the difficulties in choosing the most appropriate behavioural markers to assess the efficacy of possible treatments, (III) the limited knowledge we still have of the neurobiological bases of ASD pathology and of its aetiology, and (IV) the complexity of ASD itself, including a highly heterogeneous group of disorders sometimes with markedly different symptoms (therefore unlikely to be treated with the same approaches). Second, we give a critical overview of the most relevant advances in designing treatments for ASD, focusing on the most commonly used animal model, the laboratory mouse. We include pharmacological and non-pharmacological approaches, underlining their specific advantages, but also their current limitations especially in relation to the problems discussed before. Finally, we highlight the theoretical (e.g. the combination of multiple rather than single treatments) and methodological (e.g. use of single-gene mouse models) approaches that seem more promising to us, suggesting various strategies that can be adopted to simplify the complex field of research on treatments for ASD.

摘要

近年来,针对自闭症谱系障碍(ASD)治疗方法的研发开展了大量令人瞩目的研究。这项工作主要基于啮齿动物模型,采用了多种基因和环境操纵手段。不幸的是,由于该领域研究特有的各种问题,为ASD确定合适治疗方法的任务极具挑战性。在此,我们首先讨论这些问题,包括:(I)存在大量啮齿动物模型(其有效性往往缺乏普遍共识);(II)选择最合适的行为标记来评估可能治疗方法的疗效存在困难;(III)我们对ASD病理学及其病因的神经生物学基础的了解仍然有限;以及(IV)ASD本身的复杂性,包括一组高度异质性的疾病,有时症状明显不同(因此不太可能用相同的方法治疗)。其次,我们对ASD治疗设计中最相关的进展进行批判性综述,重点关注最常用的动物模型——实验室小鼠。我们涵盖了药理学和非药理学方法,强调了它们的特定优势,但也指出了它们目前的局限性,特别是与之前讨论的问题相关的局限性。最后,我们强调了对我们来说似乎更有前景的理论(例如多种而非单一治疗方法的联合)和方法学(例如使用单基因小鼠模型)方法,提出了可以采用的各种策略,以简化ASD治疗研究这一复杂领域。

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