Qiu Zhihai, Guo Jinghui, Kala Shashwati, Zhu Jiejun, Xian Quanxiang, Qiu Weibao, Li Guofeng, Zhu Ting, Meng Long, Zhang Rui, Chan Hsiao Chang, Zheng Hairong, Sun Lei
Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR 999077, P. R. China.
Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR 999077, P. R. China; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China.
iScience. 2019 Nov 22;21:448-457. doi: 10.1016/j.isci.2019.10.037. Epub 2019 Oct 23.
Ultrasound brain stimulation is a promising modality for probing brain function and treating brain disease non-invasively and with high spatiotemporal resolution. However, the mechanism underlying its effects remains unclear. Here, we examine the role that the mouse piezo-type mechanosensitive ion channel component 1 (Piezo1) plays in mediating the in vitro effects of ultrasound in mouse primary cortical neurons and a neuronal cell line. We show that ultrasound alone could activate heterologous and endogenous Piezo1, initiating calcium influx and increased nuclear c-Fos expression in primary neurons but not when pre-treated with a Piezo1 inhibitor. We also found that ultrasound significantly increased the expression of the important proteins phospho-CaMKII, phospho-CREB, and c-Fos in a neuronal cell line, but Piezo1 knockdown significantly reduced this effect. Our findings demonstrate that the activity of mechanosensitive ion channels such as Piezo1 stimulated by ultrasound is an important contributor to its ability to stimulate cells in vitro.
超声脑刺激是一种很有前景的方法，可用于无创且具有高时空分辨率地探测脑功能和治疗脑部疾病。然而，其作用的潜在机制仍不清楚。在这里，我们研究了小鼠压电型机械敏感离子通道组分1（Piezo1）在介导超声对小鼠原代皮层神经元和神经元细胞系的体外作用中所起的作用。我们发现，单独的超声可激活异源和内源性Piezo1，引发原代神经元中的钙内流并增加核c-Fos表达，但在用Piezo1抑制剂预处理时则不会。我们还发现，超声显著增加了神经元细胞系中重要蛋白磷酸化CaMKII、磷酸化CREB和c-Fos的表达，但Piezo1基因敲低显著降低了这种作用。我们的研究结果表明，超声刺激的诸如Piezo1等机械敏感离子通道的活性是其在体外刺激细胞能力的重要贡献因素。
