背景:刺激初级运动皮层(M1)的高频重复经颅磁刺激(rTMS)是一种替代方法,改善帕金森病(PD)运动症状的辅助治疗。然而,rTMS的高频率是否与PD运动症状的改善呈正相关,目前尚不确定。通过控制其他参数,疾病动物模型可能有助于比较不同高频rTMS的神经保护作用。
目的:当前的探索性研究旨在比较四种常见的高频rTMS(5、10、15和20Hz)和iTBS(一种特殊形式的高频rTMS)的保护作用,并探索动物PD模型上的最佳高频rTMS。
方法:在MPTP/丙磺舒诱导的慢性PD模型中高频应用rTMS(每周两次,共5周)后,5种方案对运动行为以及多巴胺能神经元变性水平的影响被鉴定。进一步探讨了潜在的分子机制。
结果:我们发现rTMS的所有高频对PD模型的运动功能都有不同程度的保护作用。其中,10、15和20HzrTMS干预通过保护黑质纹状体多巴胺神经元诱导了相当的运动功能保留。脑源性神经营养因子(BDNF)的增强,多巴胺转运蛋白(DAT),和囊泡单胺转运蛋白2(VMAT-2)以及黑质纹状体中TNF-α和IL-1β的抑制参与了该过程。iTBS的疗效不如上述三种方案。5HzrTMS协议的效果最弱。
结论:结合本研究结果和rTMS可能引起的副作用,我们得出的结论是,10Hz可能是使用rTMS治疗保留PD模型运动功能的最佳刺激频率。
BACKGROUND: High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson\'s disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS.
OBJECTIVE: The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high-frequency rTMS) and explore the optimal high-frequency rTMS on an animal PD model.
METHODS: Following high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid-induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored.
RESULTS: We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2) and the suppression of TNF-α and IL-1β in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest.
CONCLUSIONS: Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.