Decrease in newly generated oligodendrocytes leads to motor dysfunctions and changed myelin structures that can be rescued by transplanted cells.
NG2-glia in the adult brain are known to proliferate and differentiate into mature and myelinating oligodendrocytes throughout lifetime. However, the role of these newly generated oligodendrocytes in the adult brain still remains little understood. Here we took advantage of the Sox10-iCreERT2x CAG-eGFP x Esco2fl/flmouse line in which we can specifically ablate proliferating NG2-glia in adult animals. Surprisingly, we observed that the generation of new oligodendrocytes in the adult brain was severely affected, although the number of NG2-glia remained stable due to the enhanced proliferation of non-recombined cells. This lack of oligodendrogenesis led to the elongation of the nodes of Ranvier as well as the associated paranodes, which could be locally rescued by myelinating oligodendrocytes differentiated from transplanted NG2-glia deriving from wildtype mice. Repetitive measurements of conduction velocity in the corpus callosum of awake animals revealed a progressive deceleration specifically in the mice lacking adult oligodendrogenesis that resulted in progressive motor deficits. In summary, here we demonstrated for the first time that axon function is not only controlled by the reliable organization of myelin, but also requires a dynamic and continuous generation of new oligodendrocytes in the adult brain. GLIA 2016;64:2201-2218.
Physiological Genomics, Biomedical Center, Ludwig-Maximilians University, Munich, Germany.|Institute of Stem Cell Research, Helmholtz Zentrum, Neuherberg, Germany.|Graduate School of Systemic Neurosciences, Ludwig-Maximilians University, Munich, Germany.
Sarah
S
Schneider
División de Neurosciencias, Universidad Pablo de Olavide, Seville, Spain.
Agnès
A
Gruart
Physiological Genomics, Biomedical Center, Ludwig-Maximilians University, Munich, Germany.|Institute of Stem Cell Research, Helmholtz Zentrum, Neuherberg, Germany.
Sofia
S
Grade
Physiological Genomics, Biomedical Center, Ludwig-Maximilians University, Munich, Germany.
Yina
Y
Zhang
Physiological Genomics, Biomedical Center, Ludwig-Maximilians University, Munich, Germany.
Stephan
S
Kröger
Molecular Physiology, Center of Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland, Homburg, Germany.
Frank
F
Kirchhoff
Department of Genes and Behavior, MPI for Biophysical Chemistry, Göttingen, Germany.
Gregor
G
Eichele
División de Neurosciencias, Universidad Pablo de Olavide, Seville, Spain.
José M
JM
Delgado García
Physiological Genomics, Biomedical Center, Ludwig-Maximilians University, Munich, Germany. leda.dimou@lrz.uni-muenchen.de.|Institute of Stem Cell Research, Helmholtz Zentrum, Neuherberg, Germany. leda.dimou@lrz.uni-muenchen.de.|Graduate School of Systemic Neurosciences, Ludwig-Maximilians University, Munich, Germany. leda.dimou@lrz.uni-muenchen.de.|Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. leda.dimou@lrz.uni-muenchen.de.
Leda
L
Dimou
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D003337:Corpus Callosum / Q000473:pathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009069:Movement Disorders / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D009185:Myelin Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009431:Neural Conduction / Q000502:physiology; D009457:Neuroglia / Q000502:physiology* / Q000637:transplantation*; D009836:Oligodendroglia / Q000473:pathology*; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism; D016138:Walking
C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse
NG2-glia; adult brain; differentiation; oligodendrogenesis; proliferation