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

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.

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.

Metrics

  • 2,847
    views
  • 431
    downloads
  • 36
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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
  10. Wendy B Macklin
(2018)
Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone
eLife 7:e34783.
https://doi.org/10.7554/eLife.34783

Share this article

https://doi.org/10.7554/eLife.34783

Further reading

    1. Neuroscience
    Omowumi Kayode
    Insight

    Investigating how the production of insulin is regulated in fruit flies reveals surprising insights that may help to better understand how this process unfolds in humans.

    1. Neuroscience
    Lenia Amaral, Xiaosha Wang ... Ella Striem-Amit
    Research Article

    Research on brain plasticity, particularly in the context of deafness, consistently emphasizes the reorganization of the auditory cortex. But to what extent do all individuals with deafness show the same level of reorganization? To address this question, we examined the individual differences in functional connectivity (FC) from the deprived auditory cortex. Our findings demonstrate remarkable differentiation between individuals deriving from the absence of shared auditory experiences, resulting in heightened FC variability among deaf individuals, compared to more consistent FC in the hearing group. Notably, connectivity to language regions becomes more diverse across individuals with deafness. This does not stem from delayed language acquisition; it is found in deaf native signers, who are exposed to natural language since birth. However, comparing FC diversity between deaf native signers and deaf delayed signers, who were deprived of language in early development, we show that language experience also impacts individual differences, although to a more moderate extent. Overall, our research points out the intricate interplay between brain plasticity and individual differences, shedding light on the diverse ways reorganization manifests among individuals. It joins findings of increased connectivity diversity in blindness and highlights the importance of considering individual differences in personalized rehabilitation for sensory loss.