| 제목 |
Therapeutic mechanisms of repetitive transcranial magnetic stimulation |
| 소속 |
Yonsei university Wonju College of medicine, Department of Rehabilitation Medicine1, Yonsei University Wonju Colleage of Medicine, Department of Global Medical Science2, Yonsei University College of Medicine, Department and Research Institute of Rehabilitation Medicine3 |
| 저자 |
Sung Hoon Kim1†, Jun Young Park1*, Ji Hyun Kim1, Sang Yeol Yong1, Sung-Rae Cho3, Ahreum Baek1,2, Ji Yoon Jang1, Ji Sun Hong1, Min Woo Kim1 |
Introduction
Repetitive transcranial magnetic stimulation (rTMS) is a nonaggressive therapy that can be used to diagnose and treat many neurological disorders. It is well known that high-frequency (> 3 Hz) stimulation generally results in facilitation, while low-frequency (< 1 Hz) rTMS induces reduction of synaptic efficiency. Although rTMS has been the neurobiological mechanisms underlying the effects of rTMS remain unclear. Therefore, the current study examined the differential effects of rTMS depending on frequencies in both in vitro and in vivo experimental models.
Materials and methods
Mouse neuroblastoma cells were randomly divided into three groups—sham, low-frequency (0.5 Hz) and high-frequency (10 Hz) groups—and were stimulated over three days. In high-frequency group, cell proliferation was increased via up-regulation of neurotrophic factors. Then, low-frequency and high-frequency groups were characterized by RNA-seq transcriptome analysis. Among several pathways, long-term potentiation pathway is an enriched significant pathway. Furthermore, high-frequency group induced phosphorylation of cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF) transcription via activation of calcium (Ca2+)-/calmodulin-dependent protein kinase II (CaMKII)-CREB pathway. Next, cells were differentiated with retinoic acid and established for the in vitro oxygen glucose deprivation/reoxygenation (OGD/R) condition. After OGD/R injury, cells were randomly divided into three groups—OGD/R+sham, OGD/R+low-frequency and high-frequency groups—and were stimulated with rMS on day 1. High-frequency group increased cell proliferation and reduced apoptosis in OGD/R injured cells. Furthermore, high-frequency group increased BDNF expression and synaptic plasticity via activation of Ca2+-CaMKII-CREB signaling pathway in OGD/R injured cells.
Results
Eight-week Sprague-Dawley rats were unilaterally injected with 6-hydroxydopamine (6-OHDA) into the right striatum. High-frequency of rTMS (10 Hz) was treated during four weeks in the PD rats. High-frequency of rTMS improved motor functions and preserved dopaminergic neurons from damages in the substantia nigra pars compacta and striatum by 6-OHDA administration. Furthermore, neurotrophic growth factor expression was increased in high-frequency rTMS-treated PD rats, suggesting a potential for rTMS treatment in the PD.
Conclusion
Taken together, these studies will provide a better understanding of the therapeutic mechanisms of rTMS. These mechanisms may also be applicable in neural stem cells and patient-derived induced pluripotent stem cells for future studies. |
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Expression of neurotrophic/growth factors increase after repetitive magnetic stimulation in neuroblastoma cells
Effect on the proliferation of neuroblastoma cells treated with repetitive magnetic stimulation
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