Grey matter OPCs are less mature and less sensitive to IFN gamma than white matter OPCs: consequences for remyelination

Dennis H Lentferink, Jacomien M Jongsma, Inge Werkman, Wia Baron*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Scopus)
319 Downloads (Pure)

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease characterized by the formation of demyelinated lesions in the central nervous system. At later stages of the disease repair in the form of remyelination often fails, which leads to axonal degeneration and neurological disability. For the regeneration of myelin, oligodendrocyte progenitor cells (OPCs) have to migrate, proliferate and differentiate into remyelinating oligodendrocytes. Remyelination occurs faster and is more extensive in grey matter (GM) lesions than in white matter (WM) lesions. Here, we examined differences in neonatal OPCs from GM (gmOPCs) and WM (wmOPCs), both intrinsically and in response to environmental (injury) signals. We show that gmOPCs are less mature than wmOPCs, both on morphological and on gene-expression level. Additionally, gmOPCs proliferate more and differentiate slower than wmOPCs. When exposed to astrocyte-secreted signals wmOPC, but not gmOPC, migration decreases. In addition, wmOPCs are more sensitive to the detrimental effects of IFNγ treatment on proliferation, differentiation, and process arborisation, which is potentiated by TNFα. Our results demonstrate that OPCs from GM and WM differ both intrinsically and in response to their environment, which may contribute to the difference in remyelination efficiency between GM and WM MS lesions.

Original languageEnglish
Article number2113
Number of pages15
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 1-Feb-2018

Keywords

  • MULTIPLE-SCLEROSIS LESIONS
  • OLIGODENDROCYTE PROGENITOR CELLS
  • CUPRIZONE-INDUCED DEMYELINATION
  • CENTRAL-NERVOUS-SYSTEM
  • TUMOR-NECROSIS-FACTOR
  • INTERFERON-GAMMA
  • MYELINATING OLIGODENDROCYTES
  • CORTICAL REMYELINATION
  • MONOCLONAL-ANTIBODY
  • FACTOR-ALPHA

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