Gene Expression Profile Changes in the Stimulated Rat Brain Cortex After Repetitive Transcranial Magnetic Stimulation

Overview

Journal Brain Neurorehabil

Date 2023 Feb 6

PMID 36742089

Authors

Wonjae Hwang

Joong Kyung Choi

Moon Suk Bang

Woong-Yang Park

Byung-Mo Oh

Affiliations

Soon will be listed here.

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is gaining popularity as a research tool in neuroscience; however, little is known about its molecular mechanisms of action. The present study aimed to investigate the rTMS-induced transcriptomic changes; we performed microarray messenger RNA, micro RNA, and integrated analyses to explore these molecular events. Eight adult male Sprague-Dawley rats were subjected to a single session of unilateral rTMS at 1 Hz (n = 4) or sham (n = 4). The left hemisphere was stimulated for 20 minutes. To evaluate the cumulative effect of rTMS, eight additional rats were assigned to the 1-Hz (n = 4) or sham (n = 4) rTMS groups. The left hemisphere was stimulated for 5 consecutive days using the same protocol. Microarray analysis revealed differentially expressed genes in the rat cortex after rTMS treatment. The overrepresented gene ontology categories included the positive regulation of axon extension, axonogenesis, intracellular transport, and synaptic plasticity after repeated sessions of rTMS. A single session of rTMS primarily induced changes in the early genes, and several miRNAs were significantly related to the mRNAs. Future studies are required to validate the functional significance of selected genes and refine the therapeutic use of rTMS.

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References

Ikeda T, Kobayashi S, Morimoto C . Effects of repetitive transcranial magnetic stimulation on ER stress-related genes and glutamate, γ-aminobutyric acid and glycine transporter genes in mouse brain. Biochem Biophys Rep. 2018; 17:10-16. PMC: 6234257. DOI: 10.1016/j.bbrep.2018.10.015. View

Bahrami S, Drablos F . Gene regulation in the immediate-early response process. Adv Biol Regul. 2016; 62:37-49. DOI: 10.1016/j.jbior.2016.05.001. View

Wang R, Hu Y, Song G, Hao C, Cui Y, Xia H . MiR-206 regulates neural cells proliferation and apoptosis via Otx2. Cell Physiol Biochem. 2012; 29(3-4):381-90. DOI: 10.1159/000338493. View

Lefaucheur J, Drouot X, Menard-Lefaucheur I, Zerah F, Bendib B, Cesaro P . Neurogenic pain relief by repetitive transcranial magnetic cortical stimulation depends on the origin and the site of pain. J Neurol Neurosurg Psychiatry. 2004; 75(4):612-6. PMC: 1739005. DOI: 10.1136/jnnp.2003.022236. View

Lee S, Chu K, Jung K, Kim J, Huh J, Yoon H . miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model. Ann Neurol. 2012; 72(2):269-77. DOI: 10.1002/ana.23588. View

Ljubisavljevic M, Javid A, Oommen J, Parekh K, Nagelkerke N, Shehab S . The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS) Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic-Reperfusion Injury. PLoS One. 2015; 10(10):e0139892. PMC: 4592250. DOI: 10.1371/journal.pone.0139892. View

Abe A, Numakura C, Kijima K, Hayashi M, Hashimoto T, Hayasaka K . Molecular diagnosis and clinical onset of Charcot-Marie-Tooth disease in Japan. J Hum Genet. 2011; 56(5):364-8. DOI: 10.1038/jhg.2011.20. View

Lecca D, Marangon D, Coppolino G, Menendez Mendez A, Finardi A, Dalla Costa G . MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis. Sci Rep. 2016; 6:34503. PMC: 5048305. DOI: 10.1038/srep34503. View

Valero-Cabre A, Payne B, Pascual-Leone A . Opposite impact on 14C-2-deoxyglucose brain metabolism following patterns of high and low frequency repetitive transcranial magnetic stimulation in the posterior parietal cortex. Exp Brain Res. 2006; 176(4):603-15. DOI: 10.1007/s00221-006-0639-8. View

10.

Guan W, Xu D, Ji C, Wang C, Liu Y, Tang W . Hippocampal miR-206-3p participates in the pathogenesis of depression via regulating the expression of BDNF. Pharmacol Res. 2021; 174:105932. DOI: 10.1016/j.phrs.2021.105932. View

11.

Post A, Muller M, Engelmann M, Keck M . Repetitive transcranial magnetic stimulation in rats: evidence for a neuroprotective effect in vitro and in vivo. Eur J Neurosci. 1999; 11(9):3247-54. DOI: 10.1046/j.1460-9568.1999.00747.x. View

12.

Carmichael S . Themes and strategies for studying the biology of stroke recovery in the poststroke epoch. Stroke. 2008; 39(4):1380-8. PMC: 2711539. DOI: 10.1161/STROKEAHA.107.499962. View

13.

Trippe J, Mix A, Aydin-Abidin S, Funke K, Benali A . θ burst and conventional low-frequency rTMS differentially affect GABAergic neurotransmission in the rat cortex. Exp Brain Res. 2009; 199(3-4):411-21. DOI: 10.1007/s00221-009-1961-8. View

14.

Kovacs K . Measurement of immediate-early gene activation- c-fos and beyond. J Neuroendocrinol. 2008; 20(6):665-72. DOI: 10.1111/j.1365-2826.2008.01734.x. View

15.

Lefaucheur J . Stroke recovery can be enhanced by using repetitive transcranial magnetic stimulation (rTMS). Neurophysiol Clin. 2006; 36(3):105-15. DOI: 10.1016/j.neucli.2006.08.011. View

16.

Pascual-Leone A, Valls-Sole J, Wassermann E, Hallett M . Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain. 1994; 117 ( Pt 4):847-58. DOI: 10.1093/brain/117.4.847. View

17.

OReardon J, Solvason H, Janicak P, Sampson S, Isenberg K, Nahas Z . Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry. 2007; 62(11):1208-16. DOI: 10.1016/j.biopsych.2007.01.018. View

18.

Williams A, Valdez G, Moresi V, Qi X, McAnally J, Elliott J . MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. Science. 2009; 326(5959):1549-54. PMC: 2796560. DOI: 10.1126/science.1181046. View

19.

Khedr E, Ahmed M, Fathy N, Rothwell J . Therapeutic trial of repetitive transcranial magnetic stimulation after acute ischemic stroke. Neurology. 2005; 65(3):466-8. DOI: 10.1212/01.wnl.0000173067.84247.36. View

20.

Aydin-Abidin S, Trippe J, Funke K, Eysel U, Benali A . High- and low-frequency repetitive transcranial magnetic stimulation differentially activates c-Fos and zif268 protein expression in the rat brain. Exp Brain Res. 2008; 188(2):249-61. DOI: 10.1007/s00221-008-1356-2. View