4.7 Article

Myelin repair is fostered by the corticosteroid medrysone specifically acting on astroglial subpopulations

Journal

EBIOMEDICINE
Volume 83, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.ebiom.2022.104204

Keywords

Reactive astrogliosis; Multiple sclerosis; Corticosteroids; Cuprizone; Remyelination; Subventricular zone

Funding

  1. Jurgen Manchot Stiftung
  2. Research Commission of the medical faculty of the Heinrich-Heine-University of Dusseldorf
  3. Christiane and Claudia Hempel Foundation for clinical stemcell research
  4. James and Elisabeth Cloppenburg, Peek and Cloppenburg Dusseldorf Stiftung

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This study investigates the effects of medrysone on astrocytes and stem cell niches in a chronic demyelination model. The results show that medrysone can promote the recovery of mature oligodendrocytes, myelin expression, and node formation, and enhance the co-expression of C3d/S100a10 in astrocytes.
Background Multiple sclerosis is characterised by inflammation, oligodendrocyte loss and axonal demyelination and shows an additional impact on astrocytes, and their polarization. Although a certain degree of spontaneous myelin repair can be observed, disease progression, and aging impair regeneration efforts highlighting the need to better understand glial cell dynamics to establish specific regenerative treatments. Methods Applying a chronic demyelination model, we here analysed demyelination and remyelination related effects on astrocytes and stem cell niches and studied the consequences of medrysone application on myelin repair, and astrocyte polarization. Findings Medrysone induced recovery of mature oligodendrocytes, myelin expression and node formation. In addition, C3d/S100a10 co-expression in astrocytes was enhanced. Moreover, Timp1 expression in C3d positive astrocytes revealed another astrocytic phenotype with a myelination promoting character. Interpretation Based on these findings, specific astrocyte subpopulations are suggested to act in a myelin regenerative way and manner the regulation of which can be positively modulated by this corticosteroid. Copyright (C) 2022 The Authors. Published by Elsevier B.V.

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