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001     169135
005     20240311115323.0
024 7 _ |a pmc:PMC9812791
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024 7 _ |a 10.1038/s41586-022-05534-y
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024 7 _ |a pmid:36517604
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024 7 _ |a 0028-0836
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024 7 _ |a 1476-4687
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037 _ _ |a DZNE-2023-00014
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a McNamara, Niamh B
|0 0000-0002-9769-367X
|b 0
245 _ _ |a Microglia regulate central nervous system myelin growth and integrity.
260 _ _ |a London [u.a.]
|c 2023
|b Nature Publ. Group
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
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650 _ 7 |a Transforming Growth Factor beta1
|2 NLM Chemicals
650 _ 7 |a Receptor, Transforming Growth Factor-beta Type I
|0 EC 2.7.11.30
|2 NLM Chemicals
650 _ 2 |a Central Nervous System: cytology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Myelin Sheath: metabolism
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Neurodegenerative Diseases: metabolism
|2 MeSH
650 _ 2 |a Central Nervous System: metabolism
|2 MeSH
650 _ 2 |a Axons: metabolism
|2 MeSH
650 _ 2 |a Oligodendroglia
|2 MeSH
650 _ 2 |a Central Nervous System: pathology
|2 MeSH
650 _ 2 |a Microglia: cytology
|2 MeSH
650 _ 2 |a Microglia: pathology
|2 MeSH
650 _ 2 |a Myelin Sheath: pathology
|2 MeSH
650 _ 2 |a Neurodegenerative Diseases: pathology
|2 MeSH
650 _ 2 |a Oligodendroglia: metabolism
|2 MeSH
650 _ 2 |a Oligodendroglia: pathology
|2 MeSH
650 _ 2 |a Cognition
|2 MeSH
650 _ 2 |a Transforming Growth Factor beta1: metabolism
|2 MeSH
650 _ 2 |a Receptor, Transforming Growth Factor-beta Type I: metabolism
|2 MeSH
650 _ 2 |a Lipid Metabolism
|2 MeSH
650 _ 2 |a Aging: metabolism
|2 MeSH
650 _ 2 |a Aging: pathology
|2 MeSH
700 1 _ |a Munro, David A D
|b 1
700 1 _ |a Bestard-Cuche, Nadine
|b 2
700 1 _ |a Uyeda, Akiko
|b 3
700 1 _ |a Bogie, Jeroen F J
|b 4
700 1 _ |a Hoffmann, Alana
|b 5
700 1 _ |a Holloway, Rebecca K
|0 0000-0002-9396-7776
|b 6
700 1 _ |a Molina-Gonzalez, Irene
|0 0000-0001-5966-0351
|b 7
700 1 _ |a Askew, Katharine E
|b 8
700 1 _ |a Mitchell, Stephen
|b 9
700 1 _ |a Mungall, William
|b 10
700 1 _ |a Dodds, Michael
|b 11
700 1 _ |a Dittmayer, Carsten
|b 12
700 1 _ |a Moss, Jonathan
|b 13
700 1 _ |a Rose, Jamie
|b 14
700 1 _ |a Szymkowiak, Stefan
|b 15
700 1 _ |a Amann, Lukas
|0 0000-0002-8363-373X
|b 16
700 1 _ |a McColl, Barry W
|0 0000-0002-0521-9656
|b 17
700 1 _ |a Prinz, Marco
|0 0000-0002-0349-1955
|b 18
700 1 _ |a Spires-Jones, Tara L
|0 0000-0003-2530-0598
|b 19
700 1 _ |a Stenzel, Werner
|b 20
700 1 _ |a Horsburgh, Karen
|b 21
700 1 _ |a Hendriks, Jerome J A
|0 0000-0002-7717-8582
|b 22
700 1 _ |a Pridans, Clare
|0 0000-0001-9423-557X
|b 23
700 1 _ |a Muramatsu, Rieko
|0 0000-0001-5342-7823
|b 24
700 1 _ |a Williams, Anna
|0 0000-0002-6329-382X
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700 1 _ |a Priller, Josef
|0 P:(DE-2719)2811122
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700 1 _ |a Miron, Veronique E
|0 0000-0003-1738-0647
|b 27
|e Corresponding author
773 _ _ |a 10.1038/s41586-022-05534-y
|g Vol. 613, no. 7942, p. 120 - 129
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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