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

Elife. 2018 Feb 13;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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / pathology*
  • Behavior, Animal*
  • Cell Proliferation
  • Lateral Ventricles / pathology*
  • Mice
  • Myelin Proteolipid Protein / deficiency*
  • Myelin Sheath / metabolism*
  • Oligodendrocyte Precursor Cells / physiology

Substances

  • Myelin Proteolipid Protein
  • Plp1 protein, mouse