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内源性大麻素系统作为自闭症谱系障碍治疗靶点的作用:基于行为研究的小鼠模型的启示。

The role of the endocannabinoid system as a therapeutic target for autism spectrum disorder: Lessons from behavioral studies on mouse models.

机构信息

Univ. Bordeaux, CNRS, EPHE, INCIA, UMR 5287, F-33000, Bordeaux, France.

INSERM, U1215 NeuroCentre Magendie, 146 rue Léo Saignat, 33077, Bordeaux Cedex, France.

出版信息

Neurosci Biobehav Rev. 2022 Jan;132:664-678. doi: 10.1016/j.neubiorev.2021.11.031. Epub 2021 Nov 20.

Abstract

Recent years have seen an impressive amount of research devoted to understanding the etiopathology of Autism Spectrum Disorder (ASD) and developing therapies for this syndrome. Because of the lack of biomarkers of ASD, this work has been largely based on the behavioral characterization of rodent models, based on a multitude of genetic and environmental manipulations. Here we highlight how the endocannabinoid system (ECS) has recently emerged within this context of mouse behavioral studies as an etiopathological factor in ASD and a valid potential therapeutic target. We summarize the most recent results showing alterations of the ECS in rodent models of ASD, and demonstrating ASD-like behaviors in mice with altered ECS, induced either by genetic or pharmacological manipulations. We also give a critical overview of the most relevant advances in designing treatments and novel mouse models for ASD targeting the ECS, highlighting the relevance of thorough and innovative behavioral approaches to investigate the mechanisms acting underneath the complex features of ASD.

摘要

近年来,人们投入了大量的研究来理解自闭症谱系障碍(ASD)的病因病理学,并为这种综合征开发治疗方法。由于缺乏 ASD 的生物标志物,这项工作主要基于对啮齿动物模型的行为特征的研究,这些模型基于多种遗传和环境操作。在这里,我们强调了内源性大麻素系统 (ECS) 如何在这种情况下,作为 ASD 的病因病理学因素和有效的潜在治疗靶点,从老鼠行为研究中崭露头角。我们总结了最近的结果,这些结果表明,在 ASD 的啮齿动物模型中,ECS 发生了改变,并且在通过遗传或药理学操作改变 ECS 的小鼠中表现出 ASD 样行为。我们还对设计针对 ECS 的 ASD 治疗方法和新型小鼠模型的最相关进展进行了批判性概述,强调了彻底和创新的行为方法的重要性,以研究 ASD 复杂特征背后的作用机制。

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