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Schneider, S. ; Gruart, A.* ; Grade, S. ; Zhang, Y.* ; Kroeger, S.* ; Kirchhoff, F.* ; Eichele, G.* ; Delgado Garcia, J.M.* ; Dimou, L.

Decrease in newly generated oligodendrocytes leads to motor dysfunctions and changed myelin structures that can be rescued by transplanted cells.

Glia 64, 2201-2218 (2016)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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-iCreER(T2) x CAG-eGFP x Esco2(fl/fl) mouse line in which we can specifically ablate prolif-erating 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 nonrecombined 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Ng2-glia ; Oligodendrogenesis ; Proliferation ; Differentiation ; Adult Brain; White-matter; Corpus-callosum; Cerebral-cortex; Ng2 Cells; Multiple-sclerosis; Neural Crest; Adult Brain; Axons; Progenitors; Cns
ISSN (print) / ISBN 0894-1491
e-ISSN 1098-1136
Journal Glia
Quellenangaben Volume: 64, Issue: 12, Pages: 2201-2218 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)