Endothelin signalling mediates experience-dependent myelination in the CNS

  1. Matthew Swire  Is a corresponding author
  2. Yuri Kotelevtsev
  3. David J Webb
  4. David A Lyons
  5. Charles ffrench-Constant
  1. University of Edinburgh, United Kingdom
  2. Skoltech Institute for Science and Technology, Russian Federation

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.

Data availability

Data generated from phosphorylation screen is included in supporting files - supplementary file 1

Article and author information

Author details

  1. Matthew Swire

    MRC Centre for Regenerative Medicine and MS Society Edinburgh Centre, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    mswire@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4294-4926
  2. Yuri Kotelevtsev

    Centre for Neurobiology and Brain Restoration, Skoltech Institute for Science and Technology, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  3. David J Webb

    British Heart Foundation Centre of Research Excellence, Centre of Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. David A Lyons

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1166-4454
  5. Charles ffrench-Constant

    MRC Centre for Regenerative Medicine and MS Society Edinburgh Centre, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Funding

Wellcome

  • Charles ffrench-Constant

Multiple Sclerosis Society (950)

  • Charles ffrench-Constant

Wellcome (102836/Z/13/Z)

  • David A Lyons

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal husbandry and experiments were performed under UK Home Office project licenses issued under the Animals (Scientific Procedures) Act, under project licences 60/8436, 70/8436 and 70/8748. All animal experiments were reviewed, revised and approved by the University of Edinburgh Bioresearch & Veterinary Services team.

Reviewing Editor

  1. Klaus-Armin Nave, Max Planck Institute of Experimental Medicine, Germany

Version history

  1. Received: June 19, 2019
  2. Accepted: October 26, 2019
  3. Accepted Manuscript published: October 28, 2019 (version 1)
  4. Version of Record published: November 5, 2019 (version 2)

Copyright

© 2019, Swire et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Matthew Swire
  2. Yuri Kotelevtsev
  3. David J Webb
  4. David A Lyons
  5. Charles ffrench-Constant
(2019)
Endothelin signalling mediates experience-dependent myelination in the CNS
eLife 8:e49493.
https://doi.org/10.7554/eLife.49493

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https://doi.org/10.7554/eLife.49493

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