Myelin abnormalities have been observed in autism spectrum disorder (ASD). In this study, we seek to discover myelin-related changes in the striatum, a key brain region responsible for core ASD features, using the 16p11.2 deletion (16p11.2±) mouse model of ASD. We found downregulated expression of multiple myelin genes and decreased myelin thickness in the striatum of 16p11.2± mice versus wild type controls. Moreover, given that myelin is the main reservoir of brain lipids and that increasing evidence has linked dysregulation of lipid metabolism to ASD, we performed lipidomic analysis and discovered decreased levels of certain species of sphingomyelin, hexosyl ceramide and their common precursor, ceramide, in 16p11.2± striatum, all of which are major myelin components. We further identified lack of ceramide synthase 2 as the possible reason behind the decrease in these lipid species. Taken together, our data suggest a role for myelin and myelin lipids in ASD development.

中文翻译：

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自闭症谱系障碍 16p11.2 缺失小鼠模型中纹状体髓磷脂的结构和脂质组学改变。


在自闭症谱系障碍 (ASD) 中观察到髓磷脂异常。在本研究中，我们试图使用 16p11.2 缺失 (16p11.2±) 自闭症谱系障碍小鼠模型来发现纹状体中髓磷脂相关的变化，纹状体是负责自闭症谱系障碍核心特征的关键大脑区域。我们发现与野生型对照小鼠相比，16p11.2± 小鼠纹状体中多个髓磷脂基因的表达下调，髓磷脂厚度减少。此外，鉴于髓磷脂是脑脂质的主要储存库，并且越来越多的证据表明脂质代谢失调与自闭症谱系障碍有关，我们进行了脂质组学分析，发现 16p11 中某些种类的鞘磷脂、己糖基神经酰胺及其常见前体神经酰胺的水平降低.2±纹状体，所有这些都是主要的髓磷脂成分。我们进一步确定神经酰胺合酶 2 的缺乏是这些脂质种类减少的可能原因。综上所述，我们的数据表明髓磷脂和髓磷脂脂质在 ASD 发展中的作用。