Journal
FRONTIERS IN CELLULAR NEUROSCIENCE
Volume 15, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2021.718720
Keywords
autism spectrum disorder; 16p11; 2 deletion; striatum; myelin; lipid metabolism
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Funding
- Hundred Talents Program of Sun Yat-sen University [392007]
- National Natural Science Foundation of China [81874176, 82072766]
- Shenzhen Sanming Project of Medicine [SZSM201911003]
- Shenzhen Science, Technology and Innovation Commission (SZSTI) Basic Research Program [JCYJ20190809154411427]
- UK Biotechnology Biological Sciences Research Council [BB/S000844/1, BB/S008934/1]
- Guangdong Provincial Key Laboratory of Digestive Cancer Research [2021B1212040006]
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Myelin abnormalities were found in the striatum of 16p11.2(+/-) mouse model of ASD, with downregulated expression of myelin genes and decreased myelin thickness. Lipidomic analysis revealed decreased levels of certain myelin components in the striatum, suggesting a role for myelin and myelin lipids in ASD development.
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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