Riccitelli Gianna Carla, Gironi Riccardo, Melli Giorgia, Kaelin-Lang Alain
Non-Invasive Brain Stimulation Research Unit, Institute of Clinical Neurocenter of Southern Switzerland, EOC, 6900 Lugano, Switzerland.
Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland.
Int J Mol Sci. 2025 Jan 30;26(3):1205. doi: 10.3390/ijms26031205.
Parkinson's disease (PD) neuropathology is marked by the selective loss of dopaminergic neurons in the substantia nigra pars compacta, accompanied by the widespread involvement of central and peripheral structures. Brain-derived neurotrophic factor (BDNF), a neurotrophin crucial for the survival of dopaminergic neurons, plays a pivotal role in neuronal and glial development, neuroprotection, and the modulation of synaptic plasticity. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive technique, enhances neurotransmitter release, trans-synaptic efficacy, signaling pathways, gene transcription, neuroplasticity, and neurotrophism. Evidence supports that high-frequency rTMS increases BDNF expression and improves task-specific cognitive deficits in PD patients. This article outlines a detailed protocol to investigate whether rTMS targeting the dorsolateral prefrontal cortex bilaterally induces changes in plasma BDNF levels, the plasma-derived exosomal BDNF concentration, and executive functions in individuals with PD. Identifying non-invasive interventions that effectively modulate the neurobiological mechanisms underlying cognitive and behavioral functions is critical for addressing cognitive impairments and mitigating disease progression in the PD population. This study aims to advance translational research by identifying biomarkers and developing therapeutic strategies for future applications in neurodegenerative diseases.
帕金森病（PD）的神经病理学特征是黑质致密部多巴胺能神经元的选择性丧失，并伴有中枢和外周结构的广泛受累。脑源性神经营养因子（BDNF）是一种对多巴胺能神经元存活至关重要的神经营养因子，在神经元和神经胶质发育、神经保护以及突触可塑性调节中起关键作用。重复经颅磁刺激（rTMS）是一种非侵入性技术，可增强神经递质释放、跨突触效能、信号通路、基因转录、神经可塑性和神经营养作用。有证据表明，高频rTMS可增加PD患者的BDNF表达并改善特定任务的认知缺陷。本文概述了一项详细方案，以研究双侧靶向背外侧前额叶皮层的rTMS是否会引起PD患者血浆BDNF水平、血浆来源外泌体BDNF浓度以及执行功能的变化。确定有效调节认知和行为功能背后神经生物学机制的非侵入性干预措施，对于解决PD人群的认知障碍和减缓疾病进展至关重要。本研究旨在通过识别生物标志物和开发治疗策略，推动转化研究，以便未来应用于神经退行性疾病。
