Lipid Composition Diversity of the Human Brain White Matter Tracts

Understanding the molecular basis of the structural organization of the human brain may shed light on its functional mechanism. We present spatial lipidomics analysis of human brain sections containing neocortical gray matter and two white matter regions representing two axonal tracks: the cingulum bundle and the corpus callosum. Using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) we identify lipid composition differences not only between gray and white matter but also between two axonal tracks. Results, obtained with the MALDI-MSI method, correlated with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis of these brain regions, with Spearman's correlation coefficient equal to 0.48 (the cingulum bundle vs. gray matter), 0.47 (the corpus callosum vs. gray matter), 0.33 (the cingulum bundle vs. the corpos callosum) on 75 lipids annotated in both experiments. Using UPLC-MS/MS analysis, we further identified specific lipid classes that distinguished the two white matter regions (CL, PG, LPE), while gray and white matter comparison yielded well-established differences in lipid composition between myelin-rich and myelin poor regions (CL, DG, Cholesterol). Our findings highlight the significance of in-depth molecular analysis of brain regions and enhance our comprehension of the brain's molecular composition.