Luo Jing, Feng Yuan, Hong Zhongqiu, Yin Mingyu, Zheng Haiqing, Zhang Liying, Hu Xiquan
Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Neural Regen Res. 2024 Aug 1;19(8):1772-1780. doi: 10.4103/1673-5374.389303. Epub 2023 Nov 8.
JOURNAL/nrgr/04.03/01300535-202408000-00031/figure1/v/2023-12-16T180322Z/r/image-tiff Proliferation of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage. Transcranial magnetic stimulation (TMS) has recently emerged as a tool for inducing endogenous neural stem cell regeneration, but its underlying mechanisms remain unclear. In this study, we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells. Additionally, repetitive TMS reduced the volume of cerebral infarction in a rat model of ischemic stroke caused by middle cerebral artery occlusion, improved rat cognitive function, and promoted the proliferation of neural stem cells in the ischemic penumbra. RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia. Furthermore, PCR analysis revealed that repetitive TMS promoted AKT phosphorylation, leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4. This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway, which ultimately promotes the proliferation of neural stem cells. Subsequently, we validated the effect of repetitive TMS on AKT phosphorylation. We found that repetitive TMS promoted Ca2+ influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway, thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway. These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+ influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway. This study has produced pioneering results on the intrinsic mechanism of repetitive TMS to promote neural function recovery after ischemic stroke. These results provide a strong scientific foundation for the clinical application of repetitive TMS. Moreover, repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications, but also provide an effective platform for the expansion of neural stem cells.
《期刊/nrgr/04.03/01300535 - 202408000 - 00031/图1/v/2023 - 12 - 16T180322Z/图像 - tiff》神经干细胞的增殖对于促进神经元再生和修复脑梗死损伤至关重要。经颅磁刺激（TMS）最近已成为诱导内源性神经干细胞再生的一种工具，但其潜在机制仍不清楚。在本研究中，我们发现重复经颅磁刺激能有效促进氧 - 葡萄糖剥夺的神经干细胞的增殖。此外，重复经颅磁刺激减少了大脑中动脉闭塞所致缺血性脑卒中大鼠模型的脑梗死体积，改善了大鼠认知功能，并促进了缺血半暗带神经干细胞的增殖。RNA测序发现，重复经颅磁刺激激活了脑缺血大鼠缺血半暗带中的Wnt信号通路。此外，PCR分析显示，重复经颅磁刺激促进了AKT磷酸化，导致细胞周期相关蛋白如Cdk2和Cdk4的mRNA水平升高。这种效应还与糖原合酶激酶3β/β - 连环蛋白信号通路的激活有关，最终促进神经干细胞的增殖。随后，我们验证了重复经颅磁刺激对AKT磷酸化的作用。我们发现，重复经颅磁刺激通过激活P2钙通道/钙调蛋白途径促进Ca2 +流入神经干细胞，从而促进AKT磷酸化并激活糖原合酶激酶3β/β - 连环蛋白途径。这些发现表明，重复经颅磁刺激可通过Ca2 +流入依赖的磷酸化AKT/糖原合酶激酶3β/β - 连环蛋白信号通路促进内源性神经干细胞的增殖。本研究在重复经颅磁刺激促进缺血性脑卒中后神经功能恢复的内在机制方面取得了开创性成果。这些结果为重复经颅磁刺激的临床应用提供了坚实的科学基础。此外，重复经颅磁刺激治疗不仅可能是一种支持神经发生以用于进一步治疗应用的高效且有潜力的方法，还为神经干细胞的扩增提供了一个有效的平台。
