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.
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.
Stem Cell Reports. 2023 Feb 14;18(2):519-533. doi: 10.1016/j.stemcr.2022.12.001. Epub 2023 Jan 5.
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.
中枢神经系统（CNS）脱髓鞘疾病发生于髓鞘和少突胶质细胞受损或丢失时。髓鞘的再形成和少突胶质细胞的再生可以通过存在于成人 CNS 组织中的内源性少突胶质前体细胞（OPC）来实现。我们使用脱髓鞘杯状朊病毒（CPZ）小鼠模型，证明向脱髓鞘的鼠脑中输注趋化因子 fractalkine（CX3CL1）可增加新的少突胶质细胞形成，并增强胼胝体和皮质灰质中的髓鞘再生。这是通过增加皮质灰质中的 OPC 增殖以及在胼胝体和皮质灰质中 OPC 分化和减弱小胶质细胞/巨噬细胞激活来实现的。最后，我们证明活化的 OPC 和小胶质细胞/巨噬细胞在体内表达 fractalkine 受体 CX3CR1，并且在 OPC-小胶质细胞共培养物中，fractalkine 通过调节 OPC 和小胶质细胞的生物学来增加体外少突胶质细胞分化。我们的结果表明，fractalkine 在脱髓鞘小鼠模型中具有新的促再生作用。
