title: Olig2-lineage cells preferentially differentiate into oligodendrocytes but their processes degenerate at the chronic demyelinating stage of proteolipid protein-overexpressing mouse.
abstract: In chronic demyelinating lesions of the central nervous system, insufficient generation of oligodendrocytes (OLs) is not due to a lack of oligodendrocyte precursor cells (OPCs), because the accumulation of OPCs and premyelinating OLs can be observed within these lesions. Here we sought to identify the basis for the failure of OLs to achieve terminal differentiation in chronic demyelinating lesions through the utilization of plp1-overexpressing (Plp(tg/-)) mice. These mice are characterized by progressive demyelination in young adults and chronic demyelinating lesions at more mature stages. We show that neural stem cells, which are the precursors of OL-lineage cells, are present in the Plp(tg/-) mouse brain and that their multipotentiality and ability to self-renew are comparable to those of wild-type adults in culture. Lineage-tracing experiments using a transgenic mouse line, in which an inducible Cre recombinase is knocked in at the Olig2 locus, revealed that Olig2-lineage cells preferentially differentiated into OPCs and premyelinating OLs, but not into astrocytes, in the Plp(tg/-) mouse brain. These Olig2-lineage cells matured to express myelin basic protein but after that their processes degenerated in the chronic demyelinating lesions of the Plp(tg/-) brain. These results indicate that in chronic demyelinated lesions more OL-lineage cells are produced as part of the repair process, but their processes degenerate after maturation.
authors.affiliation: Department of Physiological Sciences, School of Life Sciences, Graduate University for Advanced Studies, Kanagawa, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.forename: Hirohide
authors.initials: H
authors.lastname: Takebayashi
authors.forename: Mikito
authors.initials: M
authors.lastname: Higashi
authors.forename: Wilaiwan
authors.initials: W
authors.lastname: Wisesmith
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ono
authors.forename: Seiji
authors.initials: S
authors.lastname: Hitoshi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikenaka
mesh_terms: D000367:Age Factors; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage / Q000502:physiology*; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000378:metabolism*; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D013629:Tamoxifen; C512773:Olig2 protein, mouse; C047516:Plp1 protein, mouse; C485184:enhanced green fluorescent protein