Spatial lipidomics reveals demyelination and remyelination dynamics in the mouse brain [* Cross-Reference *]

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Opielka, Mikolaj; Urbanowicz, Krzysztof; Konieczna-Wolska, Klaudia; Müller, Elisabeth; Krajewski, Oliwier; Feucherolles, Maureen; Zhou, Qiuqin; Bienkowski, Michal; Frache, Gilles; Hopf, Carsten; Schirmer, Lucas; Rutkowska, Aleksandra; Smolenski, Ryszard T., 2026, "Spatial lipidomics reveals demyelination and remyelination dynamics in the mouse brain [* Cross-Reference *]", https://lore.list.lu/citation?persistentId=perma:LIST.WOKNCT, LIST Open Repository, V1
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Description
Myelin pathology in demyelinating diseases is accompanied by lipid remodeling that remains challenging to characterize at the spatial level using traditional mass spectrometry. We developed an optimized AP-MALDI-Orbitrap MSI pipeline, incorporating sample preparation improvements and mass recalibration, to investigate lipid dynamics in the cuprizone (CPZ) mouse model of demyelination. Dual-modality, untargeted lipid profiling was performed to map spatially resolved lipid alterations during demyelination and spontaneous remyelination in two key brain areas of male mice: corpus callosum (CC) and cortex (Ctx), with lipid identifications benchmarked against 4D-LC-TIMS-MS/MS. Demyelinated regions were identified using Black Gold II staining. Using 1 ppm mass tolerance, we annotated 154 and 133 lipids at the sum-composition level in CC and Ctx, respectively, with 60% validated by LC-MS/MS. Spatial lipid profiling revealed CPZ-induced alterations in sphingolipids, sulfatides, and glycerophospholipids, supported by reanalysis of a published snRNA-seq dataset from a mouse CPZ model. Long-chain ceramides (Cer) and hexosylceramides (HexCer) were reduced in demyelinated regions, with partial, region-specific recovery during remyelination. Short-chain sulfatides (SHexCer), sphingomyelins (SM), and seminolipids transiently increased in the CC during demyelination, while long-chain sulfatides decreased in both CC and Ctx. Additionally, we observed demyelination-induced upregulation of polyunsaturated glycerophospholipids in CC and phosphatidylinositols (PI) in cortex. Lipid subclass changes emerged as reliable markers of both demyelination and remyelination in the mouse brain. Region-specific alterations in lipid metabolism provide new insights into the processes of de- and remyelination. Notably, remyelinated fibers have a distinct lipid profile compared to intact myelin, suggesting that lipid-based therapeutic strategies could improve myelin repair. (2025-11-01)
***This entry has been automatically imported via Infodoc(ASO) CSV by LIST harvest scripts. Please refer to https://doi.org/10.1016/j.jlr.2025.100912 for the original and latest version of the dataset and data downloads*** (2026-06-09)
Subject Physics
Keyword traditional mass spectrometry, pathology in demyelinating, demyelinating diseases, diseases is accompanied, remodeling that remains
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