PMID- 29867712
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1664-2295 (Print)
IS  - 1664-2295 (Electronic)
IS  - 1664-2295 (Linking)
VI  - 9
DP  - 2018
TI  - High-Frequency Repetitive Magnetic Stimulation Enhances the Expression of 
      Brain-Derived Neurotrophic Factor Through Activation of 
      Ca(2+)-Calmodulin-Dependent Protein Kinase II-cAMP-Response Element-Binding 
      Protein Pathway.
PG  - 285
LID - 10.3389/fneur.2018.00285 [doi]
LID - 285
AB  - 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) 
      delta, and CaMKIIalpha was increased, and the expression of CaMKIIgamma was decreased in 
      high-frequency group. These genes can activate the calcium 
      (Ca(2+))-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 Ca(2+)-CaMKII-CREB 
      pathway. In conclusion, high-frequency rMS enhances the expression of BDNF by 
      activating Ca(2+)-CaMKII-CREB pathway in the Neuro-2a cells. These findings may 
      help clarify further therapeutic mechanisms of rTMS.
FAU - Baek, Ahreum
AU  - Baek A
AD  - Department of Rehabilitation Medicine, Yonsei University Wonju College of 
      Medicine, Wonju, South Korea.
AD  - Department and Research Institute of Rehabilitation Medicine, Yonsei University 
      College of Medicine, Seoul, South Korea.
FAU - Park, Eun Jee
AU  - Park EJ
AD  - Department of Rehabilitation Medicine, The Graduate School Yonsei University 
      Wonju College of Medicine, Wonju, South Korea.
FAU - Kim, Soo Yeon
AU  - Kim SY
AD  - Department of Medicine, Yonsei University Wonju College of Medicine, Wonju, South 
      Korea.
FAU - Nam, Bae-Geun
AU  - Nam BG
AD  - Department and Research Institute of Rehabilitation Medicine, Yonsei University 
      College of Medicine, Seoul, South Korea.
AD  - Graduate Program of NanoScience and Technology, Yonsei University, Seoul, South 
      Korea.
FAU - Kim, Ji Hyun
AU  - Kim JH
AD  - Department of Rehabilitation Medicine, Yonsei University Wonju College of 
      Medicine, Wonju, South Korea.
FAU - Jun, Sang Woo
AU  - Jun SW
AD  - Department of Biomedical Clinical Engineering, Yonsei University Wonju College of 
      Medicine, Wonju, South Korea.
FAU - Kim, Sung Hoon
AU  - Kim SH
AD  - Department of Rehabilitation Medicine, Yonsei University Wonju College of 
      Medicine, Wonju, South Korea.
FAU - Cho, Sung-Rae
AU  - Cho SR
AD  - Department and Research Institute of Rehabilitation Medicine, Yonsei University 
      College of Medicine, Seoul, South Korea.
AD  - Graduate Program of NanoScience and Technology, Yonsei University, Seoul, South 
      Korea.
AD  - Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South 
      Korea.
AD  - Yonsei Stem Cell Center, Avison Biomedical Research Center, Yonsei University 
      College of Medicine, Seoul, South Korea.
AD  - Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of 
      Medicine, Seoul, South Korea.
LA  - eng
PT  - Journal Article
DEP - 20180507
PL  - Switzerland
TA  - Front Neurol
JT  - Frontiers in neurology
JID - 101546899
PMC - PMC5949612
OTO - NOTNLM
OT  - Ca2+-calmodulin-dependent protein kinase II-cAMP-response element-binding protein 
      pathway
OT  - Neuro-2a cells
OT  - brain-derived neurotrophic factor
OT  - high-frequency
OT  - low-frequency
OT  - repetitive magnetic stimulation
EDAT- 2018/06/06 06:00
MHDA- 2018/06/06 06:01
PMCR- 2018/05/07
CRDT- 2018/06/06 06:00
PHST- 2017/10/08 00:00 [received]
PHST- 2018/04/12 00:00 [accepted]
PHST- 2018/06/06 06:00 [entrez]
PHST- 2018/06/06 06:00 [pubmed]
PHST- 2018/06/06 06:01 [medline]
PHST- 2018/05/07 00:00 [pmc-release]
AID - 10.3389/fneur.2018.00285 [doi]
PST - epublish
SO  - Front Neurol. 2018 May 7;9:285. doi: 10.3389/fneur.2018.00285. eCollection 2018.