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

Elizabeth A. Gould, Nicolas Busquet, Douglas Shepherd, Robert M. Dietz, Paco S. Herson, Fabio M.Simoes De Souza, Anan Li, Nicholas M. George, Diego Restrepo, Wendy B. Macklin

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Article numbere34783
JournaleLife
Volume7
DOIs
StatePublished - Feb 13 2018
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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