Endothelin signalling mediates experience-dependent myelination in the CNS
Experience and changes in neuronal activity can alter CNS myelination, but the signalling pathways responsible remain poorly understood. Here we define a pathway in which endothelin, signalling through the G protein-coupled receptor endothelin receptor B and PKC epsilon, regulates the number of myel...
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doaj-80f3fb0ff4664f069d6c92446f1653592021-05-05T18:02:41ZengeLife Sciences Publications LtdeLife2050-084X2019-10-01810.7554/eLife.49493Endothelin signalling mediates experience-dependent myelination in the CNSMatthew Swire0https://orcid.org/0000-0003-4294-4926Yuri Kotelevtsev1David J Webb2David A Lyons3https://orcid.org/0000-0003-1166-4454Charles ffrench-Constant4MRC Centre for Regenerative Medicine, MS Society Edinburgh Centre, University of Edinburgh, Edinburgh, United Kingdom; Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Neurobiology and Brain Restoration, Skoltech Institute for Science and Technology, Moscow, Russian FederationBritish Heart Foundation Centre of Research Excellence, Centre of Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United KingdomCentre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United KingdomMRC Centre for Regenerative Medicine, MS Society Edinburgh Centre, University of Edinburgh, Edinburgh, United KingdomExperience and changes in neuronal activity can alter CNS myelination, but the signalling pathways responsible remain poorly understood. Here we define a pathway in which endothelin, signalling through the G protein-coupled receptor endothelin receptor B and PKC epsilon, regulates the number of myelin sheaths formed by individual oligodendrocytes in mouse and zebrafish. We show that this phenotype is also observed in the prefrontal cortex of mice following social isolation, and is associated with reduced expression of vascular endothelin. Additionally, we show that increasing endothelin signalling rescues this myelination defect caused by social isolation. Together, these results indicate that the vasculature responds to changes in neuronal activity associated with experience by regulating endothelin levels, which in turn affect the myelinating capacity of oligodendrocytes. This pathway may be employed to couple the metabolic support function of myelin to activity-dependent demand and also represents a novel mechanism for adaptive myelination.https://elifesciences.org/articles/49493oligodendrocytesmyelinationendothelin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthew Swire Yuri Kotelevtsev David J Webb David A Lyons Charles ffrench-Constant |
spellingShingle |
Matthew Swire Yuri Kotelevtsev David J Webb David A Lyons Charles ffrench-Constant Endothelin signalling mediates experience-dependent myelination in the CNS eLife oligodendrocytes myelination endothelin |
author_facet |
Matthew Swire Yuri Kotelevtsev David J Webb David A Lyons Charles ffrench-Constant |
author_sort |
Matthew Swire |
title |
Endothelin signalling mediates experience-dependent myelination in the CNS |
title_short |
Endothelin signalling mediates experience-dependent myelination in the CNS |
title_full |
Endothelin signalling mediates experience-dependent myelination in the CNS |
title_fullStr |
Endothelin signalling mediates experience-dependent myelination in the CNS |
title_full_unstemmed |
Endothelin signalling mediates experience-dependent myelination in the CNS |
title_sort |
endothelin signalling mediates experience-dependent myelination in the cns |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2019-10-01 |
description |
Experience and changes in neuronal activity can alter CNS myelination, but the signalling pathways responsible remain poorly understood. Here we define a pathway in which endothelin, signalling through the G protein-coupled receptor endothelin receptor B and PKC epsilon, regulates the number of myelin sheaths formed by individual oligodendrocytes in mouse and zebrafish. We show that this phenotype is also observed in the prefrontal cortex of mice following social isolation, and is associated with reduced expression of vascular endothelin. Additionally, we show that increasing endothelin signalling rescues this myelination defect caused by social isolation. Together, these results indicate that the vasculature responds to changes in neuronal activity associated with experience by regulating endothelin levels, which in turn affect the myelinating capacity of oligodendrocytes. This pathway may be employed to couple the metabolic support function of myelin to activity-dependent demand and also represents a novel mechanism for adaptive myelination. |
topic |
oligodendrocytes myelination endothelin |
url |
https://elifesciences.org/articles/49493 |
work_keys_str_mv |
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1721458874626605056 |