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
期刊:
影响因子:
5.9
通讯作者:
Voronova, Anastassia
Voronova, Anastassia
中科院分区:
医学1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

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当髓鞘和少突胶质细胞受损或丢失时,发生中枢神经系统(CNS)的脱髓鞘病症。少突胶质细胞的再髓鞘化和再生可以从存在于成年CNS组织中的内源性少突胶质细胞前体细胞(OPC)实现。使用cuprizone小鼠模型脱髓鞘,我们表明,fractalkine(CX 3CL 1)输注到脱髓鞘的小鼠大脑增加从头少突胶质细胞的形成,并增强在胼胝体和皮质灰质髓鞘再生。这是通过增加皮质灰质中的OPC增殖以及胼胝体和皮质灰质中的OPC分化和小胶质细胞/巨噬细胞活化的减弱来实现的。最后,我们发现,激活的OPC和小胶质细胞/巨噬细胞表达fractalkine受体CX 3CR 1在体内,并在OPC-小胶质细胞共培养fractalkine增加体外少突胶质细胞分化,通过调节OPC和小胶质细胞的生物学。我们的研究结果证明了Fractalkine在脱髓鞘小鼠模型中的新的促再生作用。CX 3CR 1在小鼠和人的小胶质细胞和脱髓鞘脑中的OPCs中表达脱髓鞘损伤后的脑内Fractalkine输注增强髓鞘再生Fractalkine通过直接调节小胶质细胞和OPCs增强少突胶质细胞的发生在这里,作者证明了给予趋化因子fractalkine(CX 3CL 1)在脱髓鞘损伤后注入脑内,通过调节OPC增殖和分化以及体内小胶质细胞/巨噬细胞活化。他们进一步表明OPC和小胶质细胞在脱髓鞘的CNS中表达fractalkine受体(CX 3CR 1),并且fractalkine通过调节OPC和小胶质细胞生物学增加体外少突胶质细胞发生。
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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