Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model

Monique M A de Almeida; Adrianne E S Watson; Sana Bibi; Nicole L Dittmann; Kara Goodkey; Pedram Sharafodinzadeh; Danny Galleguillos; Maryam Nakhaei-Nejad; Jayasankar Kosaraju; Noam Steinberg; Beatrix S Wang; Tim Footz; Fabrizio Giuliani; Jing Wang; Simonetta Sipione; Julia M Edgar; Anastassia Voronova

doi:10.1016/j.stemcr.2022.12.001

Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model

Stem Cell Reports. 2023 Feb 14;18(2):519-533. doi: 10.1016/j.stemcr.2022.12.001. Epub 2023 Jan 5.

Authors

Monique M A de Almeida¹, Adrianne E S Watson², Sana Bibi³, Nicole L Dittmann¹, Kara Goodkey², Pedram Sharafodinzadeh³, Danny Galleguillos⁴, Maryam Nakhaei-Nejad⁵, Jayasankar Kosaraju⁶, Noam Steinberg⁴, Beatrix S Wang², Tim Footz³, Fabrizio Giuliani⁷, Jing Wang⁸, Simonetta Sipione⁴, Julia M Edgar⁹, Anastassia Voronova¹⁰

Affiliations

¹ Department of Medical Genetics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada; Neuroscience and Mental Health Institute, Faculty of Medicine & Dentistry, Edmonton, AB T6G 2E1, Canada.
² Department of Medical Genetics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada; Women and Children's Health Research Institute, University of Alberta, 5-083 Edmonton Clinic Health Academy, 11405 87 Avenue NW, Edmonton, AB T6G 1C9, Canada.
³ Department of Medical Genetics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
⁴ Neuroscience and Mental Health Institute, Faculty of Medicine & Dentistry, Edmonton, AB T6G 2E1, Canada; Department of Pharmacology, Faculty of Medicine & Dentistry, Edmonton, AB T6G 2H7, Canada.
⁵ Department of Medicine, Faculty of Medicine & Dentistry, Edmonton, AB T6G 2H7, Canada.
⁶ Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
⁷ Department of Medicine, Faculty of Medicine & Dentistry, Edmonton, AB T6G 2H7, Canada; Multiple Sclerosis Centre and Department of Cell Biology, Faculty of Medicine & Dentistry, Edmonton, AB T6G 2H7, Canada.
⁸ Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa Brain and Mind Research Institute, Ottawa, ON K1H 8M5, Canada.
⁹ School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
¹⁰ Department of Medical Genetics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada; Women and Children's Health Research Institute, University of Alberta, 5-083 Edmonton Clinic Health Academy, 11405 87 Avenue NW, Edmonton, AB T6G 1C9, Canada; Neuroscience and Mental Health Institute, Faculty of Medicine & Dentistry, Edmonton, AB T6G 2E1, Canada; Department of Cell Biology, Faculty of Medicine & Dentistry, Edmonton, AB T6G 2H7, Canada; Multiple Sclerosis Centre and Department of Cell Biology, Faculty of Medicine & Dentistry, Edmonton, AB T6G 2H7, Canada. Electronic address: voronova@ualberta.ca.

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.

Keywords: CX3CL1; CX3CR1; NG2; OPC; chemokine; differentiation; multiple sclerosis; myelination; neuron-glia; regeneration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / physiology
Chemokine CX3CL1
Demyelinating Diseases*
Disease Models, Animal
Mice
Mice, Inbred C57BL
Myelin Sheath
Oligodendroglia / physiology
Remyelination*

Substances

Chemokine CX3CL1

Abstract

Publication types

MeSH terms

Substances

Grants and funding