Proteomic and lipidomic profiling of demyelinating lesions identifies fatty acids as modulators in lesion recovery.
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BiBTeXAfter demyelinating injury of the central nervous system, resolution of the mounting acute inflammation is crucial for the initiation of a regenerative response. Here, we aim to identify fatty acids and lipid mediators that govern the balance of inflammatory reactions within demyelinating lesions. Using lipidomics, we identify bioactive lipids in the resolution phase of inflammation with markedly elevated levels of n-3 polyunsaturated fatty acids. Using fat-1 transgenic mice, which convert n-6 fatty acids to n-3 fatty acids, we find that reduction of the n-6/n-3 ratio decreases the phagocytic infiltrate. In addition, we observe accelerated decline of microglia/macrophages and enhanced generation of oligodendrocytes in aged mice when n-3 fatty acids are shuttled to the brain. Thus, n-3 fatty acids enhance lesion recovery and may, therefore, provide the basis for pro-regenerative medicines of demyelinating diseases in the central nervous system.
SEEK ID: http://lmmeisd-2.srv.mwn.de/publications/20
PubMed ID: 34706241
Projects: Published Datasets
Publication type: Journal
Journal: Cell Rep
Citation: Cell Rep. 2021 Oct 26;37(4):109898. doi: 10.1016/j.celrep.2021.109898.
Date Published: 26th Oct 2021
Registered Mode: by PubMed ID
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Created: 5th Jul 2024 at 09:28
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Projects: Published Datasets, Unpublished Datasets
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After demyelinating injury of the central nervous system, resolution of the mounting acute innate inflammation is crucial for the initiation of a regenerative response. To identify factors in lesion recovery after demyelination injury, we used a toxin-induced model, in which a single dose of lysolecithin is injected into the corpus callosum to induce a focal demyelinating lesion. Afterwards, we investigated the proteome of demyelinating lesions at different time points post injection (dpi) in a ...
