TY  - JOUR
AU  - McNamara, Niamh B
AU  - Munro, David A D
AU  - Bestard-Cuche, Nadine
AU  - Uyeda, Akiko
AU  - Bogie, Jeroen F J
AU  - Hoffmann, Alana
AU  - Holloway, Rebecca K
AU  - Molina-Gonzalez, Irene
AU  - Askew, Katharine E
AU  - Mitchell, Stephen
AU  - Mungall, William
AU  - Dodds, Michael
AU  - Dittmayer, Carsten
AU  - Moss, Jonathan
AU  - Rose, Jamie
AU  - Szymkowiak, Stefan
AU  - Amann, Lukas
AU  - McColl, Barry W
AU  - Prinz, Marco
AU  - Spires-Jones, Tara L
AU  - Stenzel, Werner
AU  - Horsburgh, Karen
AU  - Hendriks, Jerome J A
AU  - Pridans, Clare
AU  - Muramatsu, Rieko
AU  - Williams, Anna
AU  - Priller, Josef
AU  - Miron, Veronique E
TI  - Microglia regulate central nervous system myelin growth and integrity.
JO  - Nature 
VL  - 613
IS  - 7942
SN  - 0028-0836
CY  - London [u.a.]
PB  - Nature Publ. Group
M1  - DZNE-2023-00014
SP  - 120 - 129
PY  - 2023
AB  - 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.
KW  - Central Nervous System: cytology
KW  - Humans
KW  - Mice
KW  - Animals
KW  - Adult
KW  - Myelin Sheath: metabolism
KW  - Microglia: metabolism
KW  - Neurodegenerative Diseases: metabolism
KW  - Central Nervous System: metabolism
KW  - Axons: metabolism
KW  - Oligodendroglia
KW  - Central Nervous System: pathology
KW  - Microglia: cytology
KW  - Microglia: pathology
KW  - Myelin Sheath: pathology
KW  - Neurodegenerative Diseases: pathology
KW  - Oligodendroglia: metabolism
KW  - Oligodendroglia: pathology
KW  - Cognition
KW  - Transforming Growth Factor beta1: metabolism
KW  - Receptor, Transforming Growth Factor-beta Type I: metabolism
KW  - Lipid Metabolism
KW  - Aging: metabolism
KW  - Aging: pathology
KW  - Transforming Growth Factor beta1 (NLM Chemicals)
KW  - Receptor, Transforming Growth Factor-beta Type I (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC9812791
C6  - pmid:36517604
DO  - DOI:10.1038/s41586-022-05534-y
UR  - https://pub.dzne.de/record/169135
ER  -