Kim Hwan-Ki, Lee Dong-Won, Kim Eunmi, Jeong Inyoung, Kim Suhyun, Kim Bum-Joon, Park Hae-Chul
Department of Biomedical Sciences, College of Medicine, Korea University, Ansan 15355, Korea.
Department of Neurosurgery, Korea University Ansan Hospital, Ansan 15355, Korea.
Exp Neurobiol. 2020 Dec 31;29(6):417-424. doi: 10.5607/en20050.
The myelination of axons in the vertebrate nervous system through oligodendrocytes promotes efficient axonal conduction, which is required for the normal function of neurons. The central nervous system (CNS) can regenerate damaged myelin sheaths through the process of remyelination, but the failure of remyelination causes neurological disorders such as multiple sclerosis. In mammals, parenchymal oligodendrocyte progenitor cells (OPCs) are known to be the principal cell type responsible for remyelination in demyelinating diseases and traumatic injuries to the adult CNS. However, growing evidence suggests that neural stem cells (NSCs) are implicated in remyelination in animal models of demyelination. We have previously shown that radial glia (RG) have the potential to function as NSCs to produce oligodendrocytes in adult zebrafish. In this study, we developed a zebrafish model of adult telencephalic injury to investigate cellular and molecular mechanisms underlying the regeneration of oligodendrocytes. Using this model, we showed that telencephalic injury induced the proliferation of RG and parenchymal OPCs shortly after injury, which was followed by the regeneration of new oligodendrocytes in the adult zebrafish. We also showed that blocking Notch signaling promoted the proliferation of RG and OPCs in the normal and injured telencephalon of adult zebrafish. Taken together, our data suggest that Notch-regulated proliferation of RG and parenchymal OPCs is responsible for the regeneration of oligodendrocytes in the injured telencephalon of adult zebrafish.
在脊椎动物神经系统中，少突胶质细胞对轴突的髓鞘形成可促进高效的轴突传导，而这是神经元正常功能所必需的。中枢神经系统（CNS）可通过髓鞘再生过程修复受损的髓鞘，但髓鞘再生失败会导致诸如多发性硬化症等神经疾病。在哺乳动物中，已知实质少突胶质前体细胞（OPCs）是成年中枢神经系统脱髓鞘疾病和创伤性损伤中负责髓鞘再生的主要细胞类型。然而，越来越多的证据表明，神经干细胞（NSCs）参与了脱髓鞘动物模型中的髓鞘再生。我们之前已经表明，放射状胶质细胞（RG）有潜力作为神经干细胞在成年斑马鱼中产生少突胶质细胞。在本研究中，我们建立了一个成年斑马鱼端脑损伤模型，以研究少突胶质细胞再生的细胞和分子机制。利用该模型，我们发现端脑损伤在损伤后不久就诱导了RG和实质OPCs的增殖，随后成年斑马鱼中出现了新的少突胶质细胞的再生。我们还表明，阻断Notch信号通路可促进成年斑马鱼正常和损伤端脑中RG和OPCs的增殖。综上所述，我们的数据表明，Notch调节的RG和实质OPCs的增殖是成年斑马鱼损伤端脑少突胶质细胞再生的原因。
