Dose-Dependence of Changes in Cortical Protein Expression Induced with Repeated Transcranial Magnetic Theta-Burst Stimulation in the Rat

Dose-Dependence of Changes in Cortical Protein Expression Induced with Repeated Transcranial Magnetic Theta-Burst Stimulation in the Rat
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DOI:
10.1016/j.brs.2013.01.008
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发表时间:
2013-07
期刊:
影响因子:
7.7
通讯作者:
L. Volz;A. Benali;A. Mix;U. Neubacher;K. Funke
L. Volz;A. Benali;A. Mix;U. Neubacher;K. Funke
中科院分区:
医学1区
文献类型:
--
作者:
L. Volz;A. Benali;A. Mix;U. Neubacher;K. Funke

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背景Theta Burst刺激(TBS)通过经颅磁刺激(TMS)有效地调节人类新皮层的兴奋性,但在短时间间隔内重复应用相同的TBS方案可能不是简单的累积。我们的目的是研究多个阻断间歇(iTBS)或连续TBS(cTBS)对大鼠皮层神经元活性标记蛋白表达的影响。或cTBS-块600刺激施加到麻醉大鼠,然后免疫组织化学和Western blot analysis.ResultsThe iTBS和cTBS的效果是相似的,但略有不同,就施加的刺激的数量。谷氨酸脱羧酶(GAD 65)的65-kD亚型的表达随着每个刺激阻断而增加,而67-kD亚型的表达(GAD 67)、钙结合蛋白(CaBP)、小清蛋白(PV)和钙结合蛋白(CB)的表达以及即刻早期基因c-Fos的表达逐渐减少。这两个TBS协议增加了囊泡谷氨酸转运蛋白1(VGLUT 1)的表达与1200-1800刺激,但然后减少他们后,第4 block.ConclusionOur的研究结果表明,重复TBS elelaries没有简单的累积剂量依赖性效应的所有活动标记,但不同的配置文件与阈值特性和一个盈亏效应,特别是对标记物的抑制活性CB和GAD 67。有趣的是,体细胞活动标记物,如c-Fos(主要是兴奋性神经元)和GAD 67、CB和PV(主要是抑制性神经元),随着重复刺激而减少,而突触活动标记物主要增加,这可能是人工刺激轴突的结果。
BackgroundTheta Burst stimulation (TBS) applied via transcranial magnetic stimulation (TMS) effectively modulates human neocortical excitability but repeated applications of the same TBS protocol at short intervals may be not simply accumulative.ObjectiveOur aim was to investigate the impact of multiple blocks of either intermittent (iTBS) or continuous TBS (cTBS) on the expression of neuronal activity marker proteins in rat cortex.MethodsUp to four iTBS- or cTBS-blocks of 600 stimuli were applied to urethane-anesthetized rats followed by immunohistochemical and Western blot analyses.ResultsThe effects of iTBS and cTBS were similar but slightly differed with regard to the number of stimuli applied. The expression of the 65-kD isoform of glutamic acid decarboxylase (GAD65) increased with each stimulation block, while that of the 67-kD isoform (GAD67), and that of the calcium-binding proteins (CaBP) Parvalbumin (PV) and Calbindin (CB) and that of the immediate early gene c-Fos progressively decreased. Both TBS protocols increased the expression of the vesicular glutamate transporter 1 (VGLUT1) with 1200–1800 stimuli but then decreased them after the 4th block.ConclusionOur findings indicate that repeated TBS elicits no simple accumulative dose-dependent effect for all activity-markers but distinct profiles with threshold characteristics and a waxing-and-waning effect especially for the markers of inhibitory activity CB and GAD67. Interestingly, somatic activity markers, such as c-Fos for mainly excitatory and GAD67, CB and PV for inhibitory neurons, decreased with repeated stimulation while synaptic activity markers mainly increased which could be a result of the artificial stimulation of axons.