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小脑在自闭症谱系障碍中的作用:从社会脑到小鼠模型

The Cerebellar Involvement in Autism Spectrum Disorders: From the Social Brain to Mouse Models.

作者信息

Mapelli Lisa, Soda Teresa, D'Angelo Egidio, Prestori Francesca

机构信息

Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy.

Brain Connectivity Center, IRCCS Mondino Foundation, 27100 Pavia, Italy.

出版信息

Int J Mol Sci. 2022 Mar 31;23(7):3894. doi: 10.3390/ijms23073894.

Abstract

Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders that include a variety of forms and clinical phenotypes. This heterogeneity complicates the clinical and experimental approaches to ASD etiology and pathophysiology. To date, a unifying theory of these diseases is still missing. Nevertheless, the intense work of researchers and clinicians in the last decades has identified some ASD hallmarks and the primary brain areas involved. Not surprisingly, the areas that are part of the so-called "social brain", and those strictly connected to them, were found to be crucial, such as the prefrontal cortex, amygdala, hippocampus, limbic system, and dopaminergic pathways. With the recent acknowledgment of the cerebellar contribution to cognitive functions and the social brain, its involvement in ASD has become unmistakable, though its extent is still to be elucidated. In most cases, significant advances were made possible by recent technological developments in structural/functional assessment of the human brain and by using mouse models of ASD. Mouse models are an invaluable tool to get insights into the molecular and cellular counterparts of the disease, acting on the specific genetic background generating ASD-like phenotype. Given the multifaceted nature of ASD and related studies, it is often difficult to navigate the literature and limit the huge content to specific questions. This review fulfills the need for an organized, clear, and state-of-the-art perspective on cerebellar involvement in ASD, from its connections to the social brain areas (which are the primary sites of ASD impairments) to the use of monogenic mouse models.

摘要

自闭症谱系障碍(ASD)是一种广泛性神经发育障碍,包括多种形式和临床表型。这种异质性使ASD病因和病理生理学的临床及实验研究方法变得复杂。迄今为止,仍缺乏关于这些疾病的统一理论。然而,在过去几十年中,研究人员和临床医生的大量工作已经确定了一些ASD的特征以及涉及的主要脑区。不出所料,那些属于所谓“社会脑”的区域以及与之紧密相连的区域被发现至关重要,例如前额叶皮层、杏仁核、海马体、边缘系统和多巴胺能通路。随着最近人们认识到小脑对认知功能和社会脑的作用,其在ASD中的参与已变得明确无误,尽管其程度仍有待阐明。在大多数情况下,人类大脑结构/功能评估方面的最新技术发展以及使用ASD小鼠模型使得取得了重大进展。小鼠模型是深入了解该疾病分子和细胞对应物的宝贵工具,可作用于产生ASD样表型的特定遗传背景。鉴于ASD及其相关研究的多面性,在文献中导航并将大量内容限制在特定问题上往往很困难。这篇综述满足了对小脑在ASD中的参与情况进行有组织、清晰且最新的概述的需求,内容涵盖从小脑与社会脑区(ASD损伤的主要部位)的连接到单基因小鼠模型的应用。

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