Neurodegenerative diseases have become an increasingly serious societal problem worldwide as population aging continues. Since nerve cells in the central nervous system cannot regenerate themselves, nerve damage is often irreversible and permanent. So far, disease-modifying treatment is rarely available for most of the neurodegenerative diseases. A new technology called in situ glia-to-neuron conversion technology emerges as a potential game-changer for the treatment of neurodegenerative diseases. Recently, a research group led by Dr. Gong Chen and Dr. Wenliang Lei at Jinan University, Guangzhou, China, employed two-photon live imaging technique to lively visualize the dynamic glia-to-neuron conversion process in the mouse brain in situ. They published a research article titled Two-photon live imaging of direct glia-to-neuron conversion in mouse cortex in Neural Regeneration Research.
In this study, the authors used long-term two-photon live imaging technology to continuously capture the dynamic process of glial cells and particularly lineage-traced astroglial cells trans-differentiating into neurons in the mouse cortex in situ. The study demonstrates that astroglial cells in the mouse cortex can be directly reprogrammed into functional neurons by the neural transcription factor NeuroD1. Additionally, the authors found that the converted neurons showed dynamic neurites and growth cones and could migrate radially or tangentially to nearby locations in the mouse cortex. Furthermore, two-photon calcium imaging and patch-clamp electrophysiological recordings also found that the newly generated neurons formed functional synaptic connections with other neurons, suggesting their integration into functional neural circuits.
This work provides direct evidence for in situ glia-to-neuron conversion technology through two-photon live imaging. It also suggests that the adult mammalian brain possesses a high degree of plasticity in term of neural regeneration and circuit reconstruction, opening a new path for brain repair.
Dr. Zongqin Xiang, Shu He, and Rongjie Chen from Jinan University are the co-first authors of the paper, and Dr. Wenliang Lei, Dr. Gong Chen, Dr. Xiangyu Wang and Dr. Wen Li are the corresponding authors.
Link to the original research article:
Xiang Z, He S, Chen R, Liu S, Liu M, Xu L, Zheng J, Jiang Z, Ma L, Sun Y, Qin Y, Chen Y, Li W, Wang X, Chen G, Lei W (2023) Two-photon live imaging of direct glia-to-neuron conversion in mouse cortex. Neural Regen Res DOI: 10.4103/1673-5374.386401.