title: Pre-Existing Mature Oligodendrocytes Do Not Contribute to Remyelination following Toxin-Induced Spinal Cord Demyelination.
abstract: Remyelination is the regenerative response to demyelination. Although the oligodendrocyte progenitor is established as the major source of remyelinating cells, there is no conclusive evidence on whether mature, differentiated oligodendrocytes can also contribute to remyelination. Using two different inducible myelin-CreER mouse strains in which mature oligodendrocytes were prelabeled by the expression of membrane-bound Green fluorescent protein, we found that after focal spinal cord demyelination, the surrounding surviving labeled oligodendrocytes did not proliferate but remained at a consistent density. Furthermore, existing (prelabeled) oligodendrocytes showed no evidence of incorporation or migration into the lesioned area, or of process extension from the peripheral margins into the lesion. Thus, mature oligodendrocytes do not normally contribute to remyelination and are therefore not a promising target for regenerative therapy.
authors.affiliation: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Abbe H
authors.initials: AH
authors.lastname: Crawford
authors.affiliation: Wolfson Institute for Biomedical Research and Research Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Richa B
authors.initials: RB
authors.lastname: Tripathi
authors.affiliation: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Foerster
authors.affiliation: Wolfson Institute for Biomedical Research and Research Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: McKenzie
authors.affiliation: Wolfson Institute for Biomedical Research and Research Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Eleni
authors.initials: E
authors.lastname: Kougioumtzidou
authors.affiliation: Wolfson Institute for Biomedical Research and Research Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Grist
authors.affiliation: Wolfson Institute for Biomedical Research and Research Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: William D
authors.initials: WD
authors.lastname: Richardson
authors.affiliation: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom. Electronic address: rjf1000@cam.ac.uk.
authors.forename: Robin J M
authors.initials: RJ
authors.lastname: Franklin
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D017930:Genes, Reporter; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism*; D009416:Nerve Regeneration; D055495:Neurogenesis; D009836:Oligodendroglia / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D013629:Tamoxifen / Q000009:adverse effects
chemical_list: D013629:Tamoxifen