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@ARTICLE{McNamara:169135,
author = {McNamara, Niamh B and Munro, David A D and Bestard-Cuche,
Nadine and Uyeda, Akiko and Bogie, Jeroen F J and Hoffmann,
Alana and Holloway, Rebecca K and Molina-Gonzalez, Irene and
Askew, Katharine E and Mitchell, Stephen and Mungall,
William and Dodds, Michael and Dittmayer, Carsten and Moss,
Jonathan and Rose, Jamie and Szymkowiak, Stefan and Amann,
Lukas and McColl, Barry W and Prinz, Marco and Spires-Jones,
Tara L and Stenzel, Werner and Horsburgh, Karen and
Hendriks, Jerome J A and Pridans, Clare and Muramatsu, Rieko
and Williams, Anna and Priller, Josef and Miron, Veronique
E},
title = {{M}icroglia regulate central nervous system myelin growth
and integrity.},
journal = {Nature},
volume = {613},
number = {7942},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DZNE-2023-00014},
pages = {120 - 129},
year = {2023},
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.},
keywords = {Central Nervous System: cytology / Humans / Mice / Animals
/ Adult / Myelin Sheath: metabolism / Microglia: metabolism
/ Neurodegenerative Diseases: metabolism / Central Nervous
System: metabolism / Axons: metabolism / Oligodendroglia /
Central Nervous System: pathology / Microglia: cytology /
Microglia: pathology / Myelin Sheath: pathology /
Neurodegenerative Diseases: pathology / Oligodendroglia:
metabolism / Oligodendroglia: pathology / Cognition /
Transforming Growth Factor beta1: metabolism / Receptor,
Transforming Growth Factor-beta Type I: metabolism / Lipid
Metabolism / Aging: metabolism / Aging: pathology /
Transforming Growth Factor beta1 (NLM Chemicals) / Receptor,
Transforming Growth Factor-beta Type I (NLM Chemicals)},
cin = {Clinical Study Team Berlin 1},
ddc = {500},
cid = {I:(DE-2719)5000007},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC9812791},
pubmed = {pmid:36517604},
doi = {10.1038/s41586-022-05534-y},
url = {https://pub.dzne.de/record/169135},
}