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Published on: April 13, 2017
Microglia regulate central nervous system myelin growth and integrity
Niamh B McNamara1,2,3, David A D Munro1,4, Nadine Bestard-Cuche5
1UK Dementia Research Institute at The University of Edinburgh, Edinburgh, UK.
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.
Insights
Resident microglia are essential for maintaining adult central nervous system myelin health and function. Their absence leads to myelin degeneration and cognitive decline, implicating microglia in neurodegenerative diseases.
Area of Science:
- Neuroscience
- Cell Biology
Background:
- Myelin is crucial for neuronal function in the central nervous system (CNS).
- Mechanisms supporting myelin health and the role of CNS macrophages, particularly microglia, remain incompletely understood.
Purpose of the Study:
- To investigate the specific roles of microglia in maintaining myelin health throughout adulthood.
- To elucidate the mechanisms by which microglia influence myelin integrity and cognitive function.
Main Methods:
- Utilized mouse models and human samples to study microglia-myelin interactions.
- Investigated the impact of microglial absence on myelin development, maintenance, and degeneration.
- Analyzed oligodendrocyte states and lipid metabolism alterations.
Main Results:
- Microglia are dispensable for developmental myelin ensheathment but critical for adult myelin maintenance.
- Loss of microglia leads to myelin degeneration, impaired cognitive function, and altered oligodendrocyte lipid metabolism.
- The TGFβ1-TGFβR1 signaling pathway is implicated in microglial regulation of myelin health.
Conclusions:
- Resident microglia are essential for preserving myelin integrity and function in the adult CNS.
- Microglia represent a potential therapeutic target for age-related and neurodegenerative conditions affecting myelin.
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