Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model

de Almeida, M. M.A. et al. (2023) Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model. Stem Cell Reports, 18(2), pp. 519-533. (doi: 10.1016/j.stemcr.2022.12.001) (PMID:36608690) (PMCID:PMC9968989)

Abstract

Demyelinating disorders of the central nervous system (CNS) occur when myelin and oligodendrocytes are damaged or lost. Remyelination and regeneration of oligodendrocytes can be achieved from endogenous oligodendrocyte precursor cells (OPCs) that reside in the adult CNS tissue. Using a cuprizone mouse model of demyelination, we show that infusion of fractalkine (CX3CL1) into the demyelinated murine brain increases de novo oligodendrocyte formation and enhances remyelination in the corpus callosum and cortical gray matter. This is achieved by increased OPC proliferation in the cortical gray matter as well as OPC differentiation and attenuation of microglia/macrophage activation both in corpus callosum and cortical gray matter. Finally, we show that activated OPCs and microglia/macrophages express fractalkine receptor CX3CR1 in vivo, and that in OPC-microglia co-cultures fractalkine increases in vitro oligodendrocyte differentiation by modulating both OPC and microglia biology. Our results demonstrate a novel pro-regenerative role of fractalkine in a demyelinating mouse model.

• Item Type: Articles
• Additional Information: This work was funded by MS Society of Canada (3573) and CIHR operating grants (PS 166120), CIHR team grant (NEURON 161466 under the frame of Neuron Cofund), and Canada Research Chairs award in Neural Stem Cell Biology awarded to A.V., UK MS Society Grant (#37) to J.M.E., and by NSERC Discovery grant (RGPIN-2016-06343) and GlycoNet (ND-05) to S.S. M.M.A.A. received IBRO Short state grant to train in TEM by J.M.E. A.E.S.W. and S.B. were supported by the MS Society of Canada EndMS scholarships; A.E.S.W., K.G. and B.S.W. by WCHRI Scholarships; N.L.D. by the NSERC PGS-D, Brad Mates E Drive for Research Fund and the NMHI.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Edgar, Professor Julia and Alves De Almeida Carneiro, Mrs Monique Marylin
• Authors: de Almeida, M. M.A., Watson, A. E.S., Bibi, S., Dittmann, N. L., Goodkey, K., Sharafodinzadeh, P., Galleguillos, D., Nakhaei-Nejad, M., Kosaraju, J., Steinberg, N., Wang, B. S., Footz, T., Giuliani, F., Wang, J., Sipione, S., Edgar, J. M., and Voronova, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Stem Cell Reports
• Publisher: Elsevier (Cell Press)
• ISSN: 2213-6711
• ISSN (Online): 2213-6711
• Published Online: 05 January 2023
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Stem Cell Reports 18(2): 519-533
• Publisher Policy: Reproduced under a Creative Commons License