Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone
- University of Colorado Anschutz Medical Campus, United States
- Federal University of ABC, Brazil
- 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
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
- Beth Stevens, Boston Children's Hospital, Harvard Medical School, United States
Publication history
- Received: January 4, 2018
- Accepted: February 1, 2018
- Accepted Manuscript published: February 13, 2018 (version 1)
- 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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Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone
eLife 7:e34783.
https://doi.org/10.7554/eLife.34783
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