Quantification and Localisation of New Brain Lipid Synthesis Using Deuterium Oxide and High Resolution Mass Spectrometry.

Overview

Authors: Catherine Zhang¹, Jesse A Michael², Jonathan D Teo¹, Huitong Song¹, Mika T Westerhausen², Shadrack M Mutuku², Shane R Ellis², Anthony S Don¹

ORCID iDs: Mika T Westerhausen, Anthony S Don

School of Medical Sciences, Charles Perkins Centre, and Brain and Mind Centre, The University of Sydney, Camperdown, New South Wales, Australia
Molecular Horizons and School of Science, The University of Wollongong, Wollongong, New South Wales, Australia

Institutions: The University of Sydney (Australia); University of Wollongong (Australia)

Journal: Angewandte Chemie (International ed. in English), volume 65, issue 18, article e24636

Dates: received 7 November 2025; accepted 9 March 2026; published online 15 March 2026; in print 27 April 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1002/anie.202524636 · PMID 41834457 · PMCID PMC13110756 · OpenAlex W7136173412

Open access: hybrid, a free copy (OpenAlex)

Status: data only

Categories: other (modality), mouse (organism), multiple sclerosis (population), cellular / molecular (subfield)

Methods: Statistics, fMRI & imaging

Keywords: deuterium, lipid, mass spectrometry imaging, metabolism, remyelination

MeSH: Brain*, Deuterium Oxide*, Lipids*, Animals, Cuprizone, Mass Spectrometry, Mice, Myelin Sheath, Tandem Mass Spectrometry (* major topic)

Topic: Neurogenesis and neuroplasticity mechanisms (Developmental Neuroscience, Neuroscience), according to OpenAlex

Funding: National Health and Medical Research Council of Australia (2002660, 2028164); Multiple Sclerosis Australia (20‐0113, 20-0113); Australian Research Council Future Fellowship (FT190100082); Australian government Research Training Program scholarship

Citations: not cited yet (Europe PMC); 53 references in the paper

Abstract

Myelin is the lipid‐rich membrane that surrounds neuronal axons and is essential for neurological function in vertebrates. The development of therapeutics that stimulate myelin repair to treat demyelinating disorders such as multiple sclerosis is hampered by the inability to distinguish newly synthesised from pre‐existing myelin. This study aimed to develop a method to quantify and localise new myelin lipid synthesis in the mouse brain. Deuterium oxide was administered for two weeks in the drinking water of mice fed normal chow, chow containing the demyelinating toxin cuprizone, or during spontaneous remyelination following cuprizone withdrawal. Liquid chromatography‐tandem mass spectrometry and mass spectrometry imaging were used to quantify and localise the newly synthesised, deuterated lipids. While most glycerophospholipids were constitutively deuterated, deuteration of myelin‐enriched sulfatides, hexosylceramides, and phosphatidylethanolamine plasmalogens was only apparent during remyelination. Most deuterium atoms were found in the fatty acyl chains, indicative of de novo lipid synthesis. Deuterated hexosylceramide and phosphatidylethanolamine plasmalogen species were localised primarily to the corpus callosum, the white matter tract that is most heavily affected by cuprizone. The method described herein provides the means to quantify and spatially profile dynamic lipid synthesis across diverse biological contexts, including understanding myelin homeostasis and preclinical evaluation of remyelinating therapeutics.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

zenodo:17504677, at Zenodo; found in “Data Availability Statement”

Data Availability Statement

The data that support the findings of this study are openly available in Metabolomics Workbench, Study ID ST004338, DOI: 10.21228/M8655C (https://doi.org/10.21228/M8655C); and Zenodo, DOI: 10.5281/zenodo.17504677 (https://doi.org/10.5281/zenodo.17504677).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 5 keywords, 9 MeSH terms, 4 funders, 52 references.

Cite

This paper

Zhang, C., Michael, J. A., Teo, J. D., Song, H., Westerhausen, M. T., Mutuku, S. M., Ellis, S. R., & Don, A. S. (2026). Quantification and Localisation of New Brain Lipid Synthesis Using Deuterium Oxide and High Resolution Mass Spectrometry. Angewandte Chemie (International ed. in English), 65(18), e24636. https://doi.org/10.1002/anie.202524636

BibTeX

@article{zhang2026quantification, author = {Zhang, Catherine and Michael, Jesse A and Teo, Jonathan D and Song, Huitong and Westerhausen, Mika T and Mutuku, Shadrack M and Ellis, Shane R and Don, Anthony S}, title = {{Quantification and Localisation of New Brain Lipid Synthesis Using Deuterium Oxide and High Resolution Mass Spectrometry}}, journal = {Angewandte Chemie (International ed. in English)}, year = {2026}, month = mar, volume = {65}, number = {18}, pages = {e24636}, publisher = {Wiley}, issn = {1433-7851}, doi = {10.1002/anie.202524636}, url = {https://doi.org/10.1002/anie.202524636}, pmid = {41834457}, pmcid = {PMC13110756} }

RIS

TY - JOUR AU - Zhang, Catherine AU - Michael, Jesse A AU - Teo, Jonathan D AU - Song, Huitong AU - Westerhausen, Mika T AU - Mutuku, Shadrack M AU - Ellis, Shane R AU - Don, Anthony S TI - Quantification and Localisation of New Brain Lipid Synthesis Using Deuterium Oxide and High Resolution Mass Spectrometry T2 - Angewandte Chemie (International ed. in English) J2 - Angew Chem Int Ed Engl PY - 2026 DA - 2026/03/15 VL - 65 IS - 18 SP - e24636 SN - 1433-7851 PB - Wiley DO - 10.1002/anie.202524636 UR - https://doi.org/10.1002/anie.202524636 LA - en ER -

CSL-JSON

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