Structural and Lipidomic Alterations of Striatal Myelin in 16p11.2 Deletion Mouse Model of Autism Spectrum Disorder.
Structural and Lipidomic Alterations of Striatal Myelin in 16p11.2 Deletion Mouse Model of Autism Spectrum Disorder.
复制标题
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
DOI：
10.3389/fncel.2021.718720
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发表时间：
2021
影响因子：
5.3
通讯作者：
Li N
中科院分区：
文献类型：
--
作者：
Ju J;Yang X;Jiang J;Wang D;Zhang Y;Zhao X;Fang X;Liao H;Zheng L;Li S;Hou ST;Liang L;Pan Y;Li H;Li N
在自闭症谱系障碍（ASD）中已经观察到髓鞘异常。在这项研究中，我们使用16p11.2缺失（16p11.2±）ASD小鼠模型，试图发现纹状体中髓鞘相关的变化，纹状体是负责核心ASD特征的关键脑区。我们发现，与野生型对照组相比，16p11.2±小鼠纹状体中多个髓鞘基因的表达下调，髓鞘厚度降低。此外，鉴于髓鞘是脑脂质的主要储存库，并且越来越多的证据将脂质代谢失调与ASD联系起来，我们进行了脂质组学分析，发现16 p11.2 ±纹状体中某些种类的鞘磷脂、己糖基神经酰胺及其共同前体神经酰胺的水平降低，所有这些都是主要的髓鞘成分。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。总之，我们的数据表明髓鞘和髓鞘脂质在ASD发展中的作用。
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.
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影响因子：
3.3
作者：
Galvez-Contreras AY;Zarate-Lopez D;Torres-Chavez AL;Gonzalez-Perez O
通讯作者：
Gonzalez-Perez O
影响因子：
5.3
作者：
Wang, Wei;Rein, Benjamin;Yan, Zhen
通讯作者：
Yan, Zhen
影响因子：
4
作者：
Chung, Wendy K.;Roberts, Timothy P. L.;Sherr, Elliott H.;Snyder, LeeAnne Green;Spiro, John E.
通讯作者：
Spiro, John E.
影响因子：
4.6
作者：
Levy, Michal;Futerman, Anthony H.
通讯作者：
Futerman, Anthony H.
影响因子：
6.9
作者：
Baxter, A. J.;Brugha, T. S.;Scott, J. G.
通讯作者：
Scott, J. G.