Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model.
Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model.
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DOI:
10.1016/j.stemcr.2022.12.001
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发表时间:
2023-02-14
影响因子:
5.9
通讯作者:
Voronova, Anastassia
中科院分区:
文献类型:
--
作者:
de Almeida, Monique M. A.;Watson, Adrianne E. S.;Bibi, Sana;Dittmann, Nicole L.;Goodkey, Kara;Sharafodinzadeh, Pedram;Galleguillos, Danny;Nakhaei-Nejad, Maryam;Kosaraju, Jayasankar;Steinberg, Noam;Wang, Beatrix S.;Footz, Tim;Giuliani, Fabrizio;Wang, Jing;Sipione, Simonetta;Edgar, Julia M.;Voronova, Anastassia
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. CX3CR1 is expressed in mouse and human microglia and OPCs in demyelinated brain Intracerebral fractalkine infusion after demyelinating injury enhances remyelination Fractalkine enhances oligodendrogenesis by directly regulating microglia and OPCs Here, authors demonstrate administration of the chemokine fractalkine (CX3CL1) into the brain after demyelinating injury enhances oligodendrocyte and myelin regeneration by modulating OPC proliferation and differentiation as well as microglia/macrophage activation in vivo. They further show OPCs and microglia express fractalkine receptor (CX3CR1) in the demyelinated CNS and that fractalkine increases in vitro oligodendrogenesis by modulating both OPC and microglia biology.
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影响因子:
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作者:
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通讯作者:
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