College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin, 300071, China.
Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China.
Neurotherapeutics. 2019 Oct;16(4):1210-1224. doi: 10.1007/s13311-019-00732-5.
In this study, we have, for the first time, demonstrated the beneficial effects of transcranial magneto-acoustic stimulation (TMAS), a technique based on focused ultrasound stimulation within static magnetic field, on the learning and memory abilities and neuroplasticity of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). Our results showed that chronic TMAS treatment (2 weeks) improved the outcome of Morris water maze, long-term potentiation (LTP), and dendritic spine densities in the dentate gyrus (DG) region of the hippocampus of PD model mice. To further investigate into the underlying mechanisms of these beneficial effects by TMAS, we quantified the proteins in the hippocampus that regulated neuroplasticity. Results showed that the level of postsynaptic density protein 95 was elevated in the brain of TMAS-treated PD model mice while the level of synaptophysin (SYP) did not show any change. We further quantified proteins that mediated neuroplasticity mechanisms, such as brain-derived neurotrophic factor (BDNF) and other important proteins that mediated neuroplasticity. Results showed that TMAS treatment elevated the levels of BDNF, cAMP response element-binding protein (CREB), and protein kinase B (p-Akt) in the PD model mouse hippocampus, but not in the non-PD mouse hippocampus. These results suggest that the beneficial effects on the neuroplasticity of PD model mice treated with TMAS could possibly be conducted through postsynaptic regulations and mediated by BDNF.
在这项研究中，我们首次证明了经颅磁声刺激（TMAS）的有益效果，TMAS 是一种基于静磁场中聚焦超声刺激的技术，对帕金森病（PD）的 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）小鼠模型的学习和记忆能力及神经可塑性具有有益效果。我们的结果表明，慢性 TMAS 治疗（2 周）改善了 PD 模型小鼠水迷宫、长时程增强（LTP）和海马齿状回（DG）区树突棘密度的结果。为了进一步研究 TMAS 产生这些有益效果的潜在机制，我们定量了海马中调节神经可塑性的蛋白质。结果表明，TMAS 治疗后 PD 模型小鼠大脑中的突触后密度蛋白 95 水平升高，而突触小泡蛋白（SYP）水平没有变化。我们进一步定量了介导神经可塑性机制的蛋白质，如脑源性神经营养因子（BDNF）和其他介导神经可塑性的重要蛋白质。结果表明，TMAS 治疗提高了 PD 模型小鼠海马中的 BDNF、cAMP 反应元件结合蛋白（CREB）和蛋白激酶 B（p-Akt）水平，但在非 PD 小鼠海马中没有变化。这些结果表明，TMAS 治疗对 PD 模型小鼠神经可塑性的有益效果可能是通过突触后调节和 BDNF 介导的。
