Truong Thi-Thuyet, Huang Chih-Chung, Chiu Wen-Tai
Department of Biomedical Engineering, National Cheng Kung University, Tainan 701401, Taiwan.
Department of Biomedical Engineering, National Cheng Kung University, Tainan 701401, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan 701401, Taiwan.
Ultrasonics. 2025 Feb;146:107499. doi: 10.1016/j.ultras.2024.107499. Epub 2024 Oct 28.
Endoplasmic reticulum (ER) stress is associated with oxidative stress, which is integral to the development of various pathological conditions, including neurodegenerative disorders. In this study, using NSC-34-a hybrid cell line established by fusing motor neuron-rich embryonic spinal cord cells with mouse neuroblastoma cells-we investigated the effects of low-intensity pulsed ultrasound (LIPUS) stimulation on oxidative (reactive oxygen species)/ER stress-induced neurodegeneration. An ultrasound transducer with a center frequency of 1.15 MHz and a spatial peak temporal average intensity of 357 mW/cm was used for delivering ultrasound (for 8 min, via a water-filled tube) to motor neuron cells seeded in a plastic culture dish. LIPUS stimulation significantly increased the level of the antiapoptotic protein B-cell lymphoma 2 (BCL-2) and inhibited the expression of apoptosis-associated proteins such as BCL-2-associated X protein (BAX), CCAAT/enhancer-binding protein-homologous protein (CHOP), and caspase-12, thus extending the survival of motor neurons. LIPUS stimulation also enhanced Ca signaling and activated the Ca-dependent transcription factors as nuclear factor of activated T cells (NFAT) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Furthermore, LIPUS stimulation induced the activation of the serine/threonine kinase protein kinase B (AKT). Thus, LIPUS stimulation prevented oxidative/ER stress-mediated mitochondrial dysfunction. In conclusion, as a safe and noninvasive method, LIPUS stimulation can facilitate further development of ultrasound neuromodulation as a tool for neuroscience research.
内质网（ER）应激与氧化应激相关，氧化应激是包括神经退行性疾病在内的各种病理状况发展的一个组成部分。在本研究中，我们使用NSC - 34（一种通过将富含运动神经元的胚胎脊髓细胞与小鼠神经母细胞瘤细胞融合而建立的杂交细胞系），研究了低强度脉冲超声（LIPUS）刺激对氧化（活性氧）/内质网应激诱导的神经退行性变的影响。使用中心频率为1.15 MHz、空间峰值时间平均强度为357 mW/cm的超声换能器，通过充满水的管子向接种在塑料培养皿中的运动神经元细胞输送超声（持续8分钟）。LIPUS刺激显著提高了抗凋亡蛋白B细胞淋巴瘤2（BCL - 2）的水平，并抑制了凋亡相关蛋白如BCL - 2相关X蛋白（BAX）、CCAAT/增强子结合蛋白同源蛋白（CHOP）和半胱天冬酶 - 12的表达，从而延长了运动神经元的存活时间。LIPUS刺激还增强了钙信号传导，并激活了钙依赖性转录因子，如活化T细胞核因子（NFAT）和活化B细胞核因子κB（NF - κB）。此外，LIPUS刺激诱导了丝氨酸/苏氨酸激酶蛋白激酶B（AKT）的激活。因此，LIPUS刺激可防止氧化/内质网应激介导的线粒体功能障碍。总之，作为一种安全无创的方法，LIPUS刺激可促进超声神经调节作为神经科学研究工具的进一步发展。
