Journal Article

DZNE-2023-00014

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Microglia regulate central nervous system myelin growth and integrity.

McNamara, N. B. ; Munro, D. A. D. ; Bestard-Cuche, N. ; Uyeda, A. ; Bogie, J. F. J. ; Hoffmann, A. ; Holloway, R. K. ; Molina-Gonzalez, I. ; Askew, K. E. ; Mitchell, S. ; Mungall, W. ; Dodds, M. ; Dittmayer, C. ; Moss, J. ; Rose, J. ; Szymkowiak, S. ; Amann, L. ; McColl, B. W. ; Prinz, M. ; Spires-Jones, T. L. ; Stenzel, W. ; Horsburgh, K. ; Hendriks, J. J. A. ; Pridans, C. ; Muramatsu, R. ; Williams, A. ; Priller, J.DZNE* ; Miron, V. E. (Corresponding author)

2023
Nature Publ. Group London [u.a.]

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Please use a persistent id in citations: doi:10.1038/s41586-022-05534-y

Abstract: Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have been implicated in myelin health1, it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFβ1-TGFβR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease2,3.

Keyword(s): Central Nervous System: cytology (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Animals (MeSH) ; Adult (MeSH) ; Myelin Sheath: metabolism (MeSH) ; Microglia: metabolism (MeSH) ; Neurodegenerative Diseases: metabolism (MeSH) ; Central Nervous System: metabolism (MeSH) ; Axons: metabolism (MeSH) ; Oligodendroglia (MeSH) ; Central Nervous System: pathology (MeSH) ; Microglia: cytology (MeSH) ; Microglia: pathology (MeSH) ; Myelin Sheath: pathology (MeSH) ; Neurodegenerative Diseases: pathology (MeSH) ; Oligodendroglia: metabolism (MeSH) ; Oligodendroglia: pathology (MeSH) ; Cognition (MeSH) ; Transforming Growth Factor beta1: metabolism (MeSH) ; Receptor, Transforming Growth Factor-beta Type I: metabolism (MeSH) ; Lipid Metabolism (MeSH) ; Aging: metabolism (MeSH) ; Aging: pathology (MeSH) ; Transforming Growth Factor beta1 ; Receptor, Transforming Growth Factor-beta Type I

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Contributing Institute(s):

1. Clinical Study Team Berlin Priller (Clinical Study Team Berlin 1)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2023

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Database coverage:
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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) McNamara, N. B. ; Munro, D. A. D. ; Bestard-Cuche, N. ; Uyeda, A. ; Bogie, J. F. J. ; Hoffmann, A. ; Holloway, R. K. ; Molina-Gonzalez, I. ; Askew, K. E. ; Mitchell, S. ; Mungall, W. ; Dodds, M. ; Dittmayer, C. ; Moss, J. ; Rose, J. ; Szymkowiak, S. ; Amann, L. ; McColl, B. W. ; Prinz, M. ; Spires-Jones, T. L. ; Stenzel, W. ; Horsburgh, K. ; Hendriks, J. J. A. ; Pridans, C. ; Muramatsu, R. ; Williams, A. ; Priller, J. (Last author)DZNE* ; Miron, V. E.
Author Correction: Microglia regulate central nervous system myelin growth and integrity
Nature 631(8021), E11 (2024) [10.1038/s41586-024-07696-3]2024   Files  Fulltext by Pubmed Central BibTeX | EndNote: XML, Text | RIS

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