Skolkovo Institute of Science and Technology, Moscow, Russia.
Singapore Lipidomics Incubator, Life Sciences Institute and Precision Medicine Translational Research Program, Department of Biochemistry, Yong Loo Lin School of Medicine; National University of Singapore, Singapore, Singapore.
Nat Commun. 2024 May 25;15(1):4455. doi: 10.1038/s41467-024-48734-y.
Lipids are the most abundant but poorly explored components of the human brain. Here, we present a lipidome map of the human brain comprising 75 regions, including 52 neocortical ones. The lipidome composition varies greatly among the brain regions, affecting 93% of the 419 analyzed lipids. These differences reflect the brain's structural characteristics, such as myelin content (345 lipids) and cell type composition (353 lipids), but also functional traits: functional connectivity (76 lipids) and information processing hierarchy (60 lipids). Combining lipid composition and mRNA expression data further enhances functional connectivity association. Biochemically, lipids linked with structural and functional brain features display distinct lipid class distribution, unsaturation extent, and prevalence of omega-3 and omega-6 fatty acid residues. We verified our conclusions by parallel analysis of three adult macaque brains, targeted analysis of 216 lipids, mass spectrometry imaging, and lipidome assessment of sorted murine neurons.
脂质是人类大脑中最丰富但研究甚少的成分。在这里，我们呈现了一个包含 75 个区域的人类大脑脂质组图谱，其中包括 52 个新皮层区域。脂质组的组成在脑区之间差异很大，影响了分析的 419 种脂质中的 93%。这些差异反映了大脑的结构特征，如髓鞘含量（345 种脂质）和细胞类型组成（353 种脂质），但也反映了功能特征：功能连接（76 种脂质）和信息处理层次（60 种脂质）。将脂质组成和 mRNA 表达数据相结合，进一步增强了功能连接的相关性。从生物化学角度来看，与结构和功能脑特征相关的脂质显示出不同的脂质类别分布、不饱和程度以及 ω-3 和 ω-6 脂肪酸残基的普遍性。我们通过对三只成年猕猴大脑的平行分析、216 种脂质的靶向分析、质谱成像以及分选的鼠神经元的脂质组评估，验证了我们的结论。
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