Lipidomic Uniqueness of the Human Cerebellum White Matter

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Abstract

Lipidomics is the omics technology aimed to detect and quantify the complete diversity of lipids (lipidome) in the specific sample. Despite numerous reports confirming the crucial role of lipids in the brain functions, studies of brain lipid composition are sparse and incomplete in contrast to genome and transcriptome data. Cerebellum recently emerged as a potent modulating center of neuronal plasticity of the forebrain. Moreover, cerebellum has undergone great changes during human brain evolution. Here, we studied the spatial distribution in thousands of lipid species, marking different functional hubs in cerebellar microcircuits in evolutionary lineage – macaque, chimpanzee and human. MALDI mass-spectrometry imaging demonstrated that molecular and granular layers as well as white matter of the cerebellum had unique lipid profiles. Lipidome-based hierarchical clustering of different cerebellar hubs revealed significant evolutionary differences. Remarkably, the greatest evolutionary distance in humans compared to primates was observed in the white matter lipid profile. This fact completely agrees with the significant changes in oligodendrogenesis and myelination during human brain evolution.