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Elife. 2018 Feb 13;7. pii: e34783. doi: 10.7554/eLife.34783.

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

Author information

1
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States.
2
Rocky Mountain Taste and Smell Center, University of Colorado Anschutz Medical Campus, Aurora, United States.
3
Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, United States.
4
Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, United States.
5
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, United States.
6
Pediatric Heart Lung Center, University of Colorado Anschutz Medical Campus, Aurora, United States.
7
Department of Anesthesiology, University of Colorado School of Medicine, Aurora, United States.
8
Center of Mathematics, Computation and Cognition, Federal University of ABC, Brazil.
9
Jiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, 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.

KEYWORDS:

cognition; demyelination; motor coordination; mouse; neuroscience; olfaction; oligodendrocyte; sub ventricular zone

PMID:
29436368
PMCID:
PMC5828668
DOI:
10.7554/eLife.34783
[Indexed for MEDLINE]
Free PMC Article

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