AUTHOR=Ju Jun , Yang Xiuyan , Jiang Jian , Wang Dilong , Zhang Yumeng , Zhao Xiaofeng , Fang Xiaoyi , Liao Huanquan , Zheng Lei , Li Shupeng , Hou Sheng-Tao , Liang Liyang , Pan Yihang , Li Huiliang , Li Ningning TITLE=Structural and Lipidomic Alterations of Striatal Myelin in 16p11.2 Deletion Mouse Model of Autism Spectrum Disorder JOURNAL=Frontiers in Cellular Neuroscience VOLUME=15 YEAR=2021 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2021.718720 DOI=10.3389/fncel.2021.718720 ISSN=1662-5102 ABSTRACT=

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.