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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)519-533
Number of pages15
JournalStem Cell Reports
Volume18
Issue number2
DOIs
StatePublished - Feb 14 2023
Externally publishedYes

Keywords

  • CX3CL1
  • CX3CR1
  • NG2
  • OPC
  • chemokine
  • differentiation
  • multiple sclerosis
  • myelination
  • neuron-glia
  • regeneration

ASJC Scopus subject areas

  • Genetics
  • Biochemistry
  • Cell Biology
  • Developmental Biology

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