| 제목 |
The Differential Effects of Repetitive Magnetic Stimulation on Gene Expression in neuronal cells |
| 소속 |
Yonsei University Wonju Colleage 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, The Graduate School Yonsei University Wonju, Department of Rehabilitation Medicine4, Yonsei University, Brain Korea 21 PLUS Project for Medical Science5, Yonsei University College of Medicine, Yonsei Stem Cell Center, Avison Biomedical Research Center6 |
| 저자 |
Sung Hoon Kim1†, Ji Hyun Kim1, Jun Young Park1*, Ahreum Baek1,2, Eun Jee Park4, Bae-geun Nam3, Sang Woo Jun4, Sung-Rae Cho3,5 |
Introduction
Repetitive transcranial magnetic stimulation (rTMS) can be used to various neurological disorders. Although neurobiological mechanism of rTMS is not well known. Therefore, in this study examined the global gene expression patterns depending on different frequencies of repetitive magnetic stimulation (rMS) in neuronal cells to generate a comprehensive view of the biological mechanisms.
Materials and Methods
The mouse neuroblastoma cells, Neuro-2a cells, were randomly divided into three groups – the sham group, the low- and high-frequency group– and were stimulated over three days. The low- and high-frequency groups of rMS were characterized by transcriptome array. Differentially expressed genes were analyzed using the Database of Annotation Visualization and Integrated Discovery program, which yielded a Kyoto Encyclopedia of Genes and Genomes pathway.
Results
Among several pathways, long-term potentiation (LTP) pathway is an enriched significant pathway in high-frequency compared to low-frequency of rMS. The genes were involved in LTP pathway was validated by quantitative real-time polymerase chain reaction and immunoblotting. The expression of glutamate ionotropic receptor N-Methyl D-Aspartate 1, calmodulin-dependent protein kinase II (CaMKII)δ, and CaMKIIα was increased, and CaMKIIγ was decreased in high-frequency of rMS. These genes can activate the calcium (Ca2+)- CaMKII-cAMP-response element binding protein (CREB) pathway. Furthermore, high-frequency of rMS induced phosphorylation of CREB, brain-derived neurotrophic factor transcription via activation of Ca2+-CaMKII-CREB
pathway.
Conclusion
These findings may help clarify further therapeutic mechanisms of rTMS.
Key words: Repetitive magnetic stimulation, Low-frequency, High-frequency, Ca2+-CaMKIICREB
pathway, brain-derived neurotrophic factor |
|
|
