Swire, M;
Kotelevtsev, Y;
Webb, DJ;
Lyons, DA;
Ffrench-Constant, C;
(2019)
Endothelin signalling mediates experience-dependent myelination in the CNS.
eLife
, 8
, Article e49493. 10.7554/eLife.49493.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Endothelin signalling mediates experience-dependent myelination in the CNS |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.49493 |
| Publisher version: | https://doi.org/10.7554/eLife.49493 |
| Language: | English |
| Additional information: | © 2019, Swire et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10087385 |
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