Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong, P. R. China.
Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, P. R. China.
Nat Commun. 2024 Oct 13;15(1):8837. doi: 10.1038/s41467-024-53218-0.
Microglia, the primary immune cells in the central nervous system, play a critical role in regulating neuronal function and fate through their interaction with neurons. Despite extensive research, the specific functions and mechanisms of microglia-neuron interactions remain incompletely understood. In this study, we demonstrate that microglia establish direct contact with myelinated axons at Nodes of Ranvier in the spinal cord of mice. The contact associated with neuronal activity occurs in a random scanning pattern. In response to axonal injury, microglia rapidly transform their contact into a robust wrapping form, preventing acute axonal degeneration from extending beyond the nodes. This wrapping behavior is dependent on the function of microglial P2Y12 receptors, which may be activated by ATP released through axonal volume-activated anion channels at the nodes. Additionally, voltage-gated sodium channels (NaV) and two-pore-domain potassium (K2P) channels contribute to the interaction between nodes and glial cells following injury, and inhibition of NaV delays axonal degeneration. Through in vivo imaging, our findings reveal a neuroprotective role of microglia during the acute phase of single spinal cord axon injury, achieved through neuron-glia interaction.
小胶质细胞是中枢神经系统中的主要免疫细胞，通过与神经元相互作用，在调节神经元功能和命运方面发挥着关键作用。尽管进行了广泛的研究，但小胶质细胞-神经元相互作用的具体功能和机制仍不完全清楚。在这项研究中，我们证明了小胶质细胞在小鼠脊髓的Ranvier 结处与有髓轴突建立直接接触。与神经元活动相关的接触以随机扫描模式发生。在轴突损伤的情况下，小胶质细胞迅速将其接触转变为强大的包裹形式，防止急性轴突退变从节点延伸。这种包裹行为依赖于小胶质细胞 P2Y12 受体的功能，该受体可能通过轴突容积激活阴离子通道在节点处释放的 ATP 激活。此外，电压门控钠离子通道 (NaV) 和双孔钾通道 (K2P) 在损伤后参与节点和神经胶质细胞之间的相互作用，NaV 抑制会延迟轴突退变。通过体内成像，我们的发现揭示了小胶质细胞在单一脊髓轴突损伤的急性期通过神经元-神经胶质相互作用发挥神经保护作用。
