Mosconi Matthew W, Wang Zheng, Schmitt Lauren M, Tsai Peter, Sweeney John A
Clinical Child Psychology Program and Schiefelbusch Institute for Life Span Studies, University of Kansas Lawrence, KS, USA ; Center for Autism and Developmental Disabilities, University of Texas Southwestern Dallas, TX, USA ; Department of Psychiatry, University of Texas Southwestern Dallas, TX, USA ; Department of Pediatrics, University of Texas Southwestern Dallas, TX, USA.
Center for Autism and Developmental Disabilities, University of Texas Southwestern Dallas, TX, USA ; Department of Psychiatry, University of Texas Southwestern Dallas, TX, USA.
Front Neurosci. 2015 Sep 1;9:296. doi: 10.3389/fnins.2015.00296. eCollection 2015.
The cerebellum has been repeatedly implicated in gene expression, rodent model and post-mortem studies of autism spectrum disorder (ASD). How cellular and molecular anomalies of the cerebellum relate to clinical manifestations of ASD remains unclear. Separate circuits of the cerebellum control different sensorimotor behaviors, such as maintaining balance, walking, making eye movements, reaching, and grasping. Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients' sensorimotor impairments. We will review evidence that the development of these circuits is disrupted in individuals with ASD and that their study may help elucidate the pathophysiology of sensorimotor deficits and core symptoms of the disorder. Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted. Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD.
小脑在自闭症谱系障碍（ASD）的基因表达、啮齿动物模型及尸检研究中已被反复提及。小脑的细胞和分子异常与ASD的临床表现之间的关系仍不清楚。小脑的不同回路控制着不同的感觉运动行为，如维持平衡、行走、进行眼球运动、伸手和抓握。已发现这些行为在ASD中均受损，这表明小脑的多个不同回路可能参与了患者感觉运动障碍的发病机制。我们将综述相关证据，即这些回路的发育在ASD个体中受到破坏，且对它们的研究可能有助于阐明感觉运动缺陷及该疾病核心症状的病理生理学。与ASD相关的单基因疾病的临床前研究也已确定了小脑的选择性缺陷，并记录了针对小脑时行为症状得到改善的情况。基于这些发现，我们提出，小脑回路可能被证明是有前景的治疗靶点，有望改善不同形式ASD的感觉运动及其他临床症状。
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