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Quantification and Localisation of New Brain Lipid Synthesis Using Deuterium Oxide and High Resolution Mass
Catherine Zhang1, Jesse A Michael2, Jonathan D Teo1
1School of Medical Sciences, Charles Perkins Centre, and Brain and Mind Centre, The University of Sydney, Camperdown, New South Wales, Australia.
Angewandte Chemie (International Ed. in English)
|March 16, 2026
Summary
Researchers developed a new method to track new myelin lipid synthesis in the brain. This technique distinguishes newly made myelin from existing myelin, aiding in the development of treatments for demyelinating diseases.
Area of Science:
- Neuroscience
- Biochemistry
- Lipidomics
Background:
- Myelin is crucial for neurological function, and its repair is key for treating demyelinating diseases like multiple sclerosis.
- Current methods cannot differentiate newly synthesized myelin from pre-existing myelin, hindering therapeutic development.
Purpose of the Study:
- To develop a novel method for quantifying and localizing new myelin lipid synthesis in the mouse brain.
- To assess dynamic lipid synthesis during myelin repair and homeostasis.
Main Methods:
- Administration of deuterium oxide (heavy water) to mice under different conditions (normal, cuprizone-induced demyelination, spontaneous remyelination).
- Utilized liquid chromatography-tandem mass spectrometry (LC-MS/MS) and mass spectrometry imaging (MSI) to detect and map deuterated lipids.
- Analyzed lipid species, focusing on myelin-enriched lipids like sulfatides, hexosylceramides, and phosphatidylethanolamine plasmalogens.
Main Results:
- Deuteration was observed in myelin-enriched lipids (sulfatides, hexosylceramides, phosphatidylethanolamine plasmalogens) specifically during remyelination, not in most other glycerophospholipids.
- Deuterium incorporation primarily occurred in the fatty acyl chains, indicating de novo lipid synthesis.
- Deuterated hexosylceramide and phosphatidylethanolamine plasmalogen were localized to the corpus callosum, a key white matter tract affected by demyelination.
Conclusions:
- The developed method enables quantification and spatial profiling of dynamic lipid synthesis.
- This approach is valuable for understanding myelin homeostasis and for the preclinical evaluation of therapies aimed at myelin repair.
