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

• Published in: eLife Vol. 7
• Main Authors: Gould, Elizabeth A, Busquet, Nicolas, Shepherd, Douglas, Dietz, Robert M, Herson, Paco S, Simoes de Souza, Fabio M, Li, Anan, George, Nicholas M, Restrepo, Diego, Macklin, Wendy B
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 13-02-2018; eLife Sciences Publications, Ltd
• Subjects: Axons; Cell proliferation; cognition; Corpus callosum; Cortex; demyelination; Disease; Glial stem cells; Microscopy; motor coordination; Mutation; Myelin; Myelin proteolipid protein; Neuroscience; olfaction; Olfactory bulb; oligodendrocyte; Oligodendrocytes; Progenitor cells; Rodents; sub ventricular zone; Subventricular zone; United States > US; mouse; cognition; demyelination; neuroscience; oligodendrocyte; sub ventricular zone; olfaction; motor coordination
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.34783

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
-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
-null mice. Young adult
null mice exhibited subtle but substantial behavioral alterations, indicative of an early impact of mild myelin disruption.