Effects of repetitive transcranial magnetic stimulation on ER stress-related genes and glutamate, γ-aminobutyric acid and glycine transporter genes in mouse brain.

Effects of repetitive transcranial magnetic stimulation on ER stress-related genes and glutamate, γ-aminobutyric acid and glycine transporter genes in mouse brain.
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DOI:
10.1016/j.bbrep.2018.10.015
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发表时间:
2019-03
影响因子:
2.7
通讯作者:
Morimoto C
Morimoto C
中科院分区:
其他
文献类型:
--
作者:
Ikeda T;Kobayashi S;Morimoto C

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重复经颅磁刺激(rTMS)是治疗精神疾病的一种新兴疗法。然而,rTMS治疗效果的机制仍不清楚,限制了其优化。持续效应表明疾病相关基因发生了变化,因此我们在rTMS后1,20,30或40天的不同时间对小鼠大脑中与精神疾病相关的基因进行了基因芯片和qRT-PCR分析。与假手术对照组相比,rTMS处理小鼠脑中许多基因的表达存在差异,包括编码神经递质转运蛋白(EAAT 4、GLAST、GLT-1、GAT 2、GAT 4、GLYT 1和GLYT 2上调)和内质网(ER)应激蛋白(IRE 1 α、IRE 1 β和XBP 1下调,ATF 6和GRP 78/Bip上调)的基因。在最后一次rTMS治疗后10天,还观察到许多这些基因的表达变化。在PC 12细胞中,rTMS上调GRP 78/Bip mRNA,增强对H2 O2胁迫的抵抗力。这些结果表明,rTMS差异调节与精神和神经退行性疾病相关的多个基因。这些基因表达的持续变化可能是慢性rTMS治疗效果的基础。在rTMS之后检查小鼠脑中的基因表达变化。rTMS改变了ER应激和神经递质转运蛋白基因的表达。rTMS还诱导PC 12细胞中的ER应激基因,并保护其免受H2 O2毒性。这些表达变化可能是rTMS治疗益处的基础。
Repetitive transcranial magnetic stimulation (rTMS) is an emerging therapy for the treatment of psychiatric disorders. However, the mechanisms underlying the therapeutic effects of rTMS are still unclear, limiting its optimisation. Lasting effects suggest changes in disease-related genes, so we conducted gene chip and qRT-PCR analyses of genes associated with psychiatric diseases in the mouse brain at various times following 1, 20, 30 or 40 days of rTMS. Many genes were differentially expressed in the rTMS-treated mouse brain compared to sham controls, including genes encoding neurotransmitter transporters (upregulation of EAAT4, GLAST, GLT-1, GAT2, GAT4, GLYT1 and GLYT2), and endoplasmic reticulum (ER)-stress proteins (downregulation of IRE1α, IRE1β, and XBP1, upregulation of ATF6 and GRP78/Bip). Expression changes in many of these genes were also observed 10 days after the last rTMS treatment. In PC12 cells, rTMS upregulated GRP78/Bip mRNA and enhanced resistance against H2O2 stress. These results suggest that rTMS differentially modulates multiple genes associated with psychiatric and neurodegenerative disorders. Sustained changes in the expression of these genes may underlie the therapeutic efficacy of chronic rTMS. Gene expression changes in mouse brain were examined following rTMS. rTMS altered expression of ER-stress and neurotransmitter transporter genes. rTMS also induced ER-stress genes in PC12 cells and protected against H2O2 toxicity. These expression changes may underlie the therapeutic benefits of rTMS.
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