Department of Orthopedics, The Second Affliated Hospital of Soochow University, Suzhou, China.
CNS Neurosci Ther. 2023 Jan;29(1):256-269. doi: 10.1111/cns.14000. Epub 2022 Nov 9.
Neuronal loss caused by spinal cord injury (SCI) usually contributes to irreversible motor dysfunction. Promoting neuronal regeneration and functional recovery is vital to the repair of SCI.
Astrocytes, activated by SCI with high proliferative capacity and proximity to neuronal lineage, are considered ideal cells for neuronal regeneration. As previous studies identified several small molecules for the induction of astrocyte-to-neuron, we confirmed that ginsenoside Rg1, a neuroprotective herb, could promote the direct transdifferentiation of astrocyte-to-neuron in rat.
Immunofluorescence staining showed that 26.0 ± 1.5% of the induced cells exhibited less astroglial properties and more neuronal markers with typical neuronal morphologies, reflecting 20.6 ± 0.9% of cholinergic neurons and 22.3 ± 1.9% of dopaminergic neurons. Western blot and qRT-PCR revealed that the induced cells had better antiapoptotic ability and Rg1-promoted neuronal transdifferentiation of reactive astrocytes might take effect through suppressing Notch/Stat3 signal pathway. In vivo, a revised SCI model treated by Rg1 was confirmed with faster functional recovery and less injury lesion cavity.
In summary, our study provided a novel strategy of direct transdifferentiation of endogenous rat reactive astrocytes into neurons with Rg1 and promotion of neuronal regeneration after SCI.
脊髓损伤（SCI）导致的神经元丢失通常会导致不可逆的运动功能障碍。促进神经元再生和功能恢复对于 SCI 的修复至关重要。
星形胶质细胞在 SCI 后具有高增殖能力和接近神经元谱系，被认为是神经元再生的理想细胞。由于先前的研究已经确定了几种诱导星形胶质细胞向神经元转化的小分子，我们证实人参皂苷 Rg1 这种具有神经保护作用的草药可以促进大鼠星形胶质细胞向神经元的直接转化。
免疫荧光染色显示，诱导细胞中有 26.0±1.5%表现出较少的星形胶质细胞特性和更多的神经元标志物，具有典型的神经元形态，反映出 20.6±0.9%的胆碱能神经元和 22.3±1.9%的多巴胺能神经元。Western blot 和 qRT-PCR 显示，诱导细胞具有更好的抗凋亡能力，Rg1 促进反应性星形胶质细胞向神经元的转化可能通过抑制 Notch/Stat3 信号通路发挥作用。在体内，用 Rg1 处理的改良 SCI 模型被证实具有更快的功能恢复和更小的损伤腔。
总之，我们的研究提供了一种用 Rg1 直接将内源性大鼠反应性星形胶质细胞转化为神经元的新策略，并促进了 SCI 后的神经元再生。
