High-Frequency Repetitive Magnetic Stimulation Enhances the Expression of Brain-Derived Neurotrophic Factor Through Activation of Ca2+–Calmodulin-Dependent Protein Kinase II–cAMP-Response Element-Binding Protein Pathway
Repetitive transcranial magnetic stimulation (rTMS) can be used in various neurological disorders. However, neurobiological mechanism of rTMS is not well known. Therefore, in this study, we examined the global gene expression patterns depending on different frequencies of repetitive magnetic stimula...
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| Format: | Article |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Neurology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2018.00285/full |
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| author | Ahreum Baek Ahreum Baek Eun Jee Park Soo Yeon Kim Bae-Geun Nam Bae-Geun Nam Ji Hyun Kim Sang Woo Jun Sung Hoon Kim Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho |
| author_facet | Ahreum Baek Ahreum Baek Eun Jee Park Soo Yeon Kim Bae-Geun Nam Bae-Geun Nam Ji Hyun Kim Sang Woo Jun Sung Hoon Kim Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho |
| author_sort | Ahreum Baek |
| collection | DOAJ |
| description | Repetitive transcranial magnetic stimulation (rTMS) can be used in various neurological disorders. However, neurobiological mechanism of rTMS is not well known. Therefore, in this study, we examined the global gene expression patterns depending on different frequencies of repetitive magnetic stimulation (rMS) in both undifferentiated and differentiated Neuro-2a cells to generate a comprehensive view of the biological mechanisms. The Neuro-2a cells were randomly divided into three groups—the sham (no active stimulation) group, the low-frequency (0.5 Hz stimulation) group, and high-frequency (10 Hz stimulation) group—and were stimulated 10 min for 3 days. The low- and high-frequency groups of rMS on Neuro-2a cells 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. Amphetamine addiction pathway, circadian entrainment pathway, long-term potentiation (LTP) pathway, neurotrophin signaling pathway, prolactin signaling pathway, and cholinergic synapse pathway were significantly enriched in high-frequency group compared with low-frequency group. Among these pathways, LTP pathway is relevant to rMS, thus the genes that were involved in LTP pathway were validated by quantitative real-time polymerase chain reaction and western blotting. The expression of glutamate ionotropic receptor N-methyl d-aspartate 1, calmodulin-dependent protein kinase II (CaMKII) δ, and CaMKIIα was increased, and the expression of CaMKIIγ was decreased in high-frequency group. These genes can activate the calcium (Ca2+)–CaMKII–cAMP-response element-binding protein (CREB) pathway. Furthermore, high-frequency rMS induced phosphorylation of CREB, brain-derived neurotrophic factor (BDNF) transcription via activation of Ca2+–CaMKII–CREB pathway. In conclusion, high-frequency rMS enhances the expression of BDNF by activating Ca2+–CaMKII–CREB pathway in the Neuro-2a cells. These findings may help clarify further therapeutic mechanisms of rTMS. |
| first_indexed | 2024-04-13T07:10:24Z |
| format | Article |
| id | doaj.art-a438765cde4c4c95a18a1dabac660b06 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-13T07:10:24Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj.art-a438765cde4c4c95a18a1dabac660b062022-12-22T02:56:54ZengFrontiers Media S.A.Frontiers in Neurology1664-22952018-05-01910.3389/fneur.2018.00285318169High-Frequency Repetitive Magnetic Stimulation Enhances the Expression of Brain-Derived Neurotrophic Factor Through Activation of Ca2+–Calmodulin-Dependent Protein Kinase II–cAMP-Response Element-Binding Protein PathwayAhreum Baek0Ahreum Baek1Eun Jee Park2Soo Yeon Kim3Bae-Geun Nam4Bae-Geun Nam5Ji Hyun Kim6Sang Woo Jun7Sung Hoon Kim8Sung-Rae Cho9Sung-Rae Cho10Sung-Rae Cho11Sung-Rae Cho12Sung-Rae Cho13Department of Rehabilitation Medicine, Yonsei University Wonju College of Medicine, Wonju, South KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South KoreaDepartment of Rehabilitation Medicine, The Graduate School Yonsei University Wonju College of Medicine, Wonju, South KoreaDepartment of Medicine, Yonsei University Wonju College of Medicine, Wonju, South KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South KoreaGraduate Program of NanoScience and Technology, Yonsei University, Seoul, South KoreaDepartment of Rehabilitation Medicine, Yonsei University Wonju College of Medicine, Wonju, South KoreaDepartment of Biomedical Clinical Engineering, Yonsei University Wonju College of Medicine, Wonju, South KoreaDepartment of Rehabilitation Medicine, Yonsei University Wonju College of Medicine, Wonju, South KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South KoreaGraduate Program of NanoScience and Technology, Yonsei University, Seoul, South KoreaBrain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South KoreaYonsei Stem Cell Center, Avison Biomedical Research Center, Yonsei University College of Medicine, Seoul, South KoreaRehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, South KoreaRepetitive transcranial magnetic stimulation (rTMS) can be used in various neurological disorders. However, neurobiological mechanism of rTMS is not well known. Therefore, in this study, we examined the global gene expression patterns depending on different frequencies of repetitive magnetic stimulation (rMS) in both undifferentiated and differentiated Neuro-2a cells to generate a comprehensive view of the biological mechanisms. The Neuro-2a cells were randomly divided into three groups—the sham (no active stimulation) group, the low-frequency (0.5 Hz stimulation) group, and high-frequency (10 Hz stimulation) group—and were stimulated 10 min for 3 days. The low- and high-frequency groups of rMS on Neuro-2a cells 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. Amphetamine addiction pathway, circadian entrainment pathway, long-term potentiation (LTP) pathway, neurotrophin signaling pathway, prolactin signaling pathway, and cholinergic synapse pathway were significantly enriched in high-frequency group compared with low-frequency group. Among these pathways, LTP pathway is relevant to rMS, thus the genes that were involved in LTP pathway were validated by quantitative real-time polymerase chain reaction and western blotting. The expression of glutamate ionotropic receptor N-methyl d-aspartate 1, calmodulin-dependent protein kinase II (CaMKII) δ, and CaMKIIα was increased, and the expression of CaMKIIγ was decreased in high-frequency group. These genes can activate the calcium (Ca2+)–CaMKII–cAMP-response element-binding protein (CREB) pathway. Furthermore, high-frequency rMS induced phosphorylation of CREB, brain-derived neurotrophic factor (BDNF) transcription via activation of Ca2+–CaMKII–CREB pathway. In conclusion, high-frequency rMS enhances the expression of BDNF by activating Ca2+–CaMKII–CREB pathway in the Neuro-2a cells. These findings may help clarify further therapeutic mechanisms of rTMS.http://journal.frontiersin.org/article/10.3389/fneur.2018.00285/fullrepetitive magnetic stimulationlow-frequencyhigh-frequencyCa2+–calmodulin-dependent protein kinase II–cAMP-response element-binding protein pathwaybrain-derived neurotrophic factorNeuro-2a cells |
| spellingShingle | Ahreum Baek Ahreum Baek Eun Jee Park Soo Yeon Kim Bae-Geun Nam Bae-Geun Nam Ji Hyun Kim Sang Woo Jun Sung Hoon Kim Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho High-Frequency Repetitive Magnetic Stimulation Enhances the Expression of Brain-Derived Neurotrophic Factor Through Activation of Ca2+–Calmodulin-Dependent Protein Kinase II–cAMP-Response Element-Binding Protein Pathway Frontiers in Neurology repetitive magnetic stimulation low-frequency high-frequency Ca2+–calmodulin-dependent protein kinase II–cAMP-response element-binding protein pathway brain-derived neurotrophic factor Neuro-2a cells |
| title | High-Frequency Repetitive Magnetic Stimulation Enhances the Expression of Brain-Derived Neurotrophic Factor Through Activation of Ca2+–Calmodulin-Dependent Protein Kinase II–cAMP-Response Element-Binding Protein Pathway |
| title_full | High-Frequency Repetitive Magnetic Stimulation Enhances the Expression of Brain-Derived Neurotrophic Factor Through Activation of Ca2+–Calmodulin-Dependent Protein Kinase II–cAMP-Response Element-Binding Protein Pathway |
| title_fullStr | High-Frequency Repetitive Magnetic Stimulation Enhances the Expression of Brain-Derived Neurotrophic Factor Through Activation of Ca2+–Calmodulin-Dependent Protein Kinase II–cAMP-Response Element-Binding Protein Pathway |
| title_full_unstemmed | High-Frequency Repetitive Magnetic Stimulation Enhances the Expression of Brain-Derived Neurotrophic Factor Through Activation of Ca2+–Calmodulin-Dependent Protein Kinase II–cAMP-Response Element-Binding Protein Pathway |
| title_short | High-Frequency Repetitive Magnetic Stimulation Enhances the Expression of Brain-Derived Neurotrophic Factor Through Activation of Ca2+–Calmodulin-Dependent Protein Kinase II–cAMP-Response Element-Binding Protein Pathway |
| title_sort | high frequency repetitive magnetic stimulation enhances the expression of brain derived neurotrophic factor through activation of ca2 calmodulin dependent protein kinase ii camp response element binding protein pathway |
| topic | repetitive magnetic stimulation low-frequency high-frequency Ca2+–calmodulin-dependent protein kinase II–cAMP-response element-binding protein pathway brain-derived neurotrophic factor Neuro-2a cells |
| url | http://journal.frontiersin.org/article/10.3389/fneur.2018.00285/full |
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