Park Su Mi, Plachez Céline, Huang Shiyong
Laboratory of Neural Circuits & Behavior, Program in Neuroscience, Hussman Institute for Autism, Baltimore, MD, United States.
Autism & Brain Development Laboratory, Program in Neuroscience, Hussman Institute for Autism, Baltimore, MD, United States.
Front Behav Neurosci. 2018 Nov 13;12:261. doi: 10.3389/fnbeh.2018.00261. eCollection 2018.
Altered neuronal connectivity has been implicated in the pathophysiology of Autism Spectrum Disorder (ASD). SLIT/ROBO signaling plays an important role in developmental processes of neuronal connectivity, including axon guidance, neuronal migration, and axonal and dendritic branching. Genetic evidence supports that , one of the genes encoding SLITs, is associated with ASD. Yet the causal link between mutation and autism symptoms has not been examined. Here we assessed ASD-associated behaviors in knockout (KO) mice. Our data showed that -KO mice exhibited reduced marble burying behaviors but normal social behaviors. In addition, -KO mice displayed hypolocomotion in the open field test and impaired motor coordination in the rotarod test. Anxiety-like behaviors were mainly observed in female KO mice assessed by three types of behavioral tests, namely, the open field test, elevated plus maze test, and light/dark box test. No differences were observed between KO and wildtype mice in recognition memory in the novel object recognition test or depression-like behavior in the tail suspension test. Taken together, loss of may result in disrupted neural circuits related to motor function and increased anxiety-like states, which are co-occurring symptoms in ASD.
神经元连接改变与自闭症谱系障碍(ASD)的病理生理学有关。SLIT/ROBO信号通路在神经元连接的发育过程中起着重要作用,包括轴突导向、神经元迁移以及轴突和树突分支。遗传证据表明,编码SLITs的基因之一与ASD有关。然而,该基因突变与自闭症症状之间的因果关系尚未得到研究。在此,我们评估了该基因敲除(KO)小鼠的ASD相关行为。我们的数据显示,该基因敲除小鼠的埋珠行为减少,但社交行为正常。此外,该基因敲除小鼠在旷场试验中表现出运动减少,在转棒试验中运动协调性受损。通过旷场试验、高架十字迷宫试验和明暗箱试验这三种行为测试评估发现,焦虑样行为主要在雌性基因敲除小鼠中观察到。在新物体识别试验中的识别记忆或尾悬试验中的抑郁样行为方面,基因敲除小鼠和野生型小鼠之间未观察到差异。综上所述,该基因的缺失可能导致与运动功能相关的神经回路破坏以及焦虑样状态增加,而这些是ASD中同时出现的症状。