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Remyelination alters the pattern of myelin in the cerebral cortex

  1. Jennifer Orthmann-Murphy  Is a corresponding author
  2. Cody L Call
  3. Gian C Molina-Castro
  4. Yu Chen Hsieh
  5. Matthew N Rasband  Is a corresponding author
  6. Peter A Calabresi
  7. Dwight E Bergles  Is a corresponding author
  1. University of Pennsylvania, United States
  2. Johns Hopkins University School of Medicine, United States
  3. Massachusetts General Hospital, United States
  4. Baylor College of Medicine, United States
Research Article
  • Cited 14
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Cite this article as: eLife 2020;9:e56621 doi: 10.7554/eLife.56621

Abstract

Destruction of oligodendrocytes and myelin sheaths in cortical gray matter profoundly alters neural activity and is associated with cognitive disability in multiple sclerosis (MS). Myelin can be restored by regenerating oligodendrocytes from resident progenitors; however, it is not known whether regeneration restores the complex myelination patterns in cortical circuits. Here we performed time lapse in vivo two photon imaging in somatosensory cortex of adult mice to define the kinetics and specificity of myelin regeneration after acute oligodendrocyte ablation. These longitudinal studies revealed that the pattern of myelination in cortex changed dramatically after regeneration, as new oligodendrocytes were formed in different locations and new sheaths were often established along axon segments previously lacking myelin. Despite the dramatic increase in axonal territory available, oligodendrogenesis was persistently impaired in deeper cortical layers that experienced higher gliosis. Repeated reorganization of myelin patterns in MS may alter circuit function and contribute to cognitive decline.

Data availability

All data generated or analyzed in this study are included in the manuscript. Source code for analysis and figure generation are located at: https//github.com/clcall/Orthmann-Murphy_Call_etal_2020_Elife

Article and author information

Author details

  1. Jennifer Orthmann-Murphy

    Neurology, University of Pennsylvania, Philadelphia, United States
    For correspondence
    Jennifer.Orthmann-Murphy@pennmedicine.upenn.edu
    Competing interests
    No competing interests declared.
  2. Cody L Call

    Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2254-4298
  3. Gian C Molina-Castro

    Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0700-4042
  4. Yu Chen Hsieh

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    Competing interests
    No competing interests declared.
  5. Matthew N Rasband

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    For correspondence
    rasband@bcm.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8184-2477
  6. Peter A Calabresi

    Neurology, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    Peter A Calabresi, PI on grants to JHU from Biogen and Annexon and has received consulting fees for serving on scientific advisory boards for Biogen and Disarm Therapeutics.1147.
  7. Dwight E Bergles

    The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
    For correspondence
    dbergles@jhmi.edu
    Competing interests
    Dwight E Bergles, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7133-7378

Funding

Conrad N. Hilton Foundation

  • Jennifer Orthmann-Murphy

National Multiple Sclerosis Society

  • Jennifer Orthmann-Murphy

National Science Foundation (Graduate Research Fellowship)

  • Cody L Call

National Science Foundation (Graduate Research Fellowship)

  • Gian C Molina-Castro

National Institutes of Health (NS051509)

  • Dwight E Bergles

National Institutes of Health (NS050274)

  • Dwight E Bergles

National Institutes of Health (NS080153)

  • Dwight E Bergles

Dr. Miriam and Sheldon G Adelson Medical Research Foundation

  • Dwight E Bergles

National Multiple Sclerosis Society

  • Peter A Calabresi

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 experimentation: This study was performed in accordance with the recommendations provided in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments and procedures were approved by the Johns Hopkins Institutional Care and Use Committee (protocols: MO17M268, MO17M338). All surgery was performed under isoflurane anesthesia and every effort was made to minimize suffering.

Reviewing Editor

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

Publication history

  1. Received: March 4, 2020
  2. Accepted: May 22, 2020
  3. Accepted Manuscript published: May 27, 2020 (version 1)
  4. Version of Record published: June 12, 2020 (version 2)
  5. Version of Record updated: June 15, 2020 (version 3)

Copyright

© 2020, Orthmann-Murphy 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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