Program

PO1-13-29

Analysis of effects by repetitive Transcranial Magnetic Stimulation (rTMS) on Glutamate, GABA, Glycine transporters and ER stress-related genes on the mouse brain

[Speaker] Tetsurou Ikeda:1,2
1:Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Japan, 2:Clinical Immunology, Institute of Medical Science, TheUniversity of Tokyo, Japan

rTMS is a noninvasive technique to induce electric current in the brain and is supposed to be beneficial for the treatment of patients with depression, schizophrenia and neurodegenerative disorders. We reported previously that rTMS modulates monoamine transporter, dopamine receptor 2, circadian rhythm-related genes and HSP70. However, the mechanisms underlying the effects of rTMS are still unclear. We analyzed the changes in mRNA expression in mouse brain that occurred after rTMS with real time PCR. Following 20 days of rTMS, many genes were differentially expressed in the mouse brain. Up-regulation of Glutamate transporters (EAAT4, GLAST and GLT1), GABA transporters (GAT1 and GAT4) and Glycine transporters (GYLT1 and GLYT2) mRNA expression levels were observed after 20 days rTMS. Surprisingly, with 10 days rest after 20 days rTMS, up-regulation of Glutamate transporters (EAAC1, EAAT4, GLAST and GLT1), GABA transporters (GAT1, GAT2, GAT3 and GAT4) and Glycine transporters (GYLT1 and GLYT2) mRNA expression levels were observed. ATF6 and GRP78 (Bip) mRNA expression levels were up-regulated after transient and chronic rTMS. IRE1, Perk and XBP1 mRNA expression levels were down-regulated after transient and chronic rTMS. Interestingly, ATF6, GRP78 (Bip), IRE1, IRE1 α, Perk and XBP1 mRNA expression levels were down-regulated with 10 days rest after 20 days rTMS. In PC12 cells, an up-regulation of GRP78 (Bip) mRNA and subsequent cell-protective effects were observed after acute and chronic rTMS. GeneChip analysis after 30 days and 40 days rTMS stimulation on mouse brain also showed the similar effects as 20days rTMS stimulation. These results indicated that the modulation of several genes may be involved in the therapeutic mechanisms of acute and chronic rTMS for patients with neuropsychiatric disorders.
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