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
Affiliations
Elizabeth A Gould
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States; Rocky Mountain Taste and Smell Center, University of Colorado Anschutz Medical Campus, Aurora, United States; Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, United States
Nicolas Busquet
Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, United States
Douglas Shepherd
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, United States; Pediatric Heart Lung Center, University of Colorado Anschutz Medical Campus, Aurora, United States
Robert M Dietz
Department of Anesthesiology, University of Colorado School of Medicine, Aurora, United States
Paco S Herson
Department of Anesthesiology, University of Colorado School of Medicine, Aurora, United States
Fabio M Simoes de Souza
Center of Mathematics, Computation and Cognition, Federal University of ABC, Brazil
Anan Li
Jiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, China
Nicholas M George
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States; Rocky Mountain Taste and Smell Center, University of Colorado Anschutz Medical Campus, Aurora, United States; Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, United States
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States; Rocky Mountain Taste and Smell Center, University of Colorado Anschutz Medical Campus, Aurora, United States; Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, United States
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States; Rocky Mountain Taste and Smell Center, University of Colorado Anschutz Medical Campus, Aurora, United States; Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, United States
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.
