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Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone

  1. Elizabeth A Gould
  2. Nicolas Busquet
  3. Douglas Shepherd
  4. Robert Dietz
  5. Paco S Herson
  6. Fabio M Simoes de Souza
  7. Anan Li
  8. Nicholas M George
  9. Diego Restrepo  Is a corresponding author
  10. Wendy B Macklin  Is a corresponding author
  1. University of Colorado Anschutz Medical Campus, United States
  2. Federal University of ABC, Brazil
  3. Xuzhou Medical University, China
Research Article
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Cite this article as: eLife 2018;7:e34783 doi: 10.7554/eLife.34783

Abstract

Myelin, the insulating sheath around axons, supports axon function. An important question is the impact of mild myelin disruption. In the absence of the myelin protein proteolipid protein (PLP1), myelin is generated but with age, axonal function/ maintenance is disrupted. Axon disruption occurs in Plp1-null mice as early as 2 months in cortical projection neurons. High-volume cellular quantification techniques revealed a region-specific increase in oligodendrocyte density in the olfactory bulb and rostral corpus callosum that increased during adulthood. A distinct proliferative response of progenitor cells was observed in the subventricular zone (SVZ), while the number and proliferation of parenchymal oligodendrocyte progenitor cells was unchanged. This SVZ proliferative response occurred prior to evidence of axonal disruption. Thus, a novel SVZ response contributes to the region-specific increase in oligodendrocytes in Plp1-null mice. Young adult Plp1-null mice exhibited subtle but substantial behavioral alterations, indicative of an early impact of mild myelin disruption.

Article and author information

Author details

  1. Elizabeth A Gould

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Nicolas Busquet

    Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Douglas Shepherd

    Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Robert Dietz

    Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Paco S Herson

    Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Fabio M Simoes de Souza

    Center of Mathematics, Computation and Cognition, Federal University of ABC, Sao Bernardo do Campo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  7. Anan Li

    Jiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Nicholas M George

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Diego Restrepo

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    For correspondence
    Diego.Restrepo@ucdenver.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4972-446X
  10. Wendy B Macklin

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    For correspondence
    wendy.macklin@ucdenver.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1252-0607

Funding

National Institutes of Health (NS25304)

  • Wendy B Macklin

National Multiple Sclerosis Society

  • Wendy B Macklin

National Institutes of Health (DC00566)

  • Diego Restrepo

National Institutes of Health (DC014253)

  • Diego Restrepo

National Institutes of Health (AG053690)

  • Douglas Shepherd

National Institutes of Health (DC012280)

  • Elizabeth A Gould

National Institutes of Health (NS099042)

  • Elizabeth A Gould

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

Ethics

Animal experimentation: All animals used in this study were treated in accordance with the University of Colorado Animal Care and Use Committee guidelines. The University of Colorado Animal Care and Use Committee approved this study under protocol numbers B-39615(05)1E and 00134.

Reviewing Editor

  1. Beth Stevens, Boston Children's Hospital, Harvard Medical School, United States

Publication history

  1. Received: January 4, 2018
  2. Accepted: February 1, 2018
  3. Accepted Manuscript published: February 13, 2018 (version 1)
  4. Version of Record published: February 27, 2018 (version 2)

Copyright

© 2018, Gould 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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