Abstract
Changes in the composition and distribution of the lipids comprising the myelin sheath surrounding neuronal axons have been under-explored in neuroinflammatory diseases such as multiple sclerosis due to the complexities in the analysis of lipids in biological tissues. The application of mass spectrometry-based molecular imaging enables the study of the molecular components of demyelinating tissue. This provides a much better understanding of the complex molecular processes involved in lipid metabolism and the underlying neuroinflammatory demyelinating processes. Uncovering alterations in the lipid profiles during the demyelination processes can potentially elucidate new molecular targets for novel MS drug therapies. We have utilized mass spectrometry imaging (MSI) of in-situ sulfatide lipids in mouse CNS tissue to reveal their spatial distribution and relative abundance. We show that they are generally confined to the white matter region of the cerebellum. We provide a molecular snapshot of lipid alterations at different disease stages of experimental autoimmune encephalomyelitis (EAE), the animal model for MS. Our results suggest that alterations in sulfatide expression are greatest prior to the onset of clinical disease symptoms and are systemic through the white matter and not restricted to the focal inflammatory lesions pathognomonic of EAE and human MS. The lipid mass maps generated by MSI provide novel insights into the dynamics of lipid alterations during neuroinflammation.
Data availability
The datasets used during the current study are available from the corresponding author upon reasonable request.
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Acknowledgements
The authors would also like to thank Dr. Erin Seeley, from the UT Mass Spectrometry Imaging center for her mentorship, MSI expertise, and assistance in performing timsTOF MS/MS lipid identification. Thank you to Dr. Grace Samenuk for her cryogenic sectioning assistance, MALDI-TOF MSI guidance, and Dr. Andrea Kelley and Dr. Madeline Colley for their MALDI expertise. This project was supported by grant NS137101 from the National Institute of Health (T.G.F., S.B.B.). Finally, the authors thank the UTSA RISE program for its research funding and professional development support.
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K.A.B.: Conducted all MSI analysis, data processing, figure generation, and manuscript writing and editing. C.C.H. performed all murine immunizations, cell culturing, disease scoring, and tissue acquisition. C.G. assisted with animal monitoring and disease scoring and carried out immunofluorescent staining. T.G.F. conceived the studies and reviewed and edited all manuscript drafts. S.B.H.B. Contributed to the design of the mass spectrometry studies, manuscript editing, and final manuscript review.
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Berlin, K.A., Huizar, C.C., Garza, C. et al. MALDI-TOF mass spectrometry imaging of sulfatide lipid expression in the CNS of mice with experimental autoimmune encephalomyelitis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41147-5
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DOI: https://doi.org/10.1038/s41598-026-41147-5
