Su Wenfeng, He Xiaowen, Lin Zhihao, Xu Jinghui, Shangguan Jianghong, Wei Zhongya, Zhao Yayu, Xing Lingyan, Gu Yun, Chen Gang
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Medical School of Nantong University, Nantong, 226001, China.
Center for Basic Medical Research, Medical School of Nantong University, Nantong, 226001, China.
Mol Neurobiol. 2025 Mar;62(3):3067-3081. doi: 10.1007/s12035-024-04460-6. Epub 2024 Sep 3.
In the vertebrate nervous system, myelination of nerve fibers is crucial for the rapid propagation of action potentials through saltatory conduction. Schwann cells-the main glial cells and myelinating cells of the peripheral nervous system-play a crucial role in myelination. Following injury during the repair of peripheral nerve injuries, a significant amount of ATP is secreted. This ATP release acts to trigger the dedifferentiation of myelinating Schwann cells into repair cells, an essential step for axon regeneration. Subsequently, to restore nerve function, these repair cells undergo redifferentiate into myelinating Schwann cells. Except for P2X4R, purine receptors such as P2X7R also play a significant role in this process. In the current study, decreased expression of P2X7R was observed after sciatic nerve injury, followed by a gradual increase to the normal level of P2X7R expression. In vivo experiments showed that the activation of P2X7R using an agonist injection promoted remyelination, while the antagonists hindered remyelination. Further, in vitro experiments supported these findings and demonstrated that P2X7R activation inhibited the proliferation of Schwann cells, but it promoted the migration and differentiation of the Schwann cells. Remyelination is a prominent feature of the nerve regeneration. In the current study, it was proposed that the manipulation of P2X7R expression in Schwann cells after nerve injury could be effective in facilitating nerve remyelination.
在脊椎动物神经系统中,神经纤维的髓鞘形成对于通过跳跃式传导快速传播动作电位至关重要。雪旺细胞——外周神经系统的主要神经胶质细胞和髓鞘形成细胞——在髓鞘形成中起关键作用。在周围神经损伤修复过程中受伤后,会分泌大量三磷酸腺苷(ATP)。这种ATP释放促使有髓鞘形成的雪旺细胞去分化为修复细胞,这是轴突再生的关键步骤。随后,为恢复神经功能,这些修复细胞会重新分化为有髓鞘形成的雪旺细胞。除P2X4R外,嘌呤受体如P2X7R在这一过程中也起重要作用。在当前研究中,观察到坐骨神经损伤后P2X7R表达下降,随后逐渐增加至P2X7R表达的正常水平。体内实验表明,使用激动剂注射激活P2X7R可促进髓鞘再生,而拮抗剂则会阻碍髓鞘再生。此外,体外实验支持了这些发现,并表明P2X7R激活会抑制雪旺细胞的增殖,但会促进雪旺细胞的迁移和分化。髓鞘再生是神经再生的一个显著特征。在当前研究中,有人提出,在神经损伤后操纵雪旺细胞中P2X7R的表达可能有助于促进神经髓鞘再生。