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人源神经元样细胞的重复性磁刺激激活 cAMP-CREB 通路。

Repetitive magnetic stimulation of human-derived neuron-like cells activates cAMP-CREB pathway.

机构信息

Klinik und Hochschulambulanz für Psychiatrie und Psychotherapie, Charité Campus Benjamin Franklin, Eschenallee 3, 14050, Berlin, Germany.

出版信息

Eur Arch Psychiatry Clin Neurosci. 2012 Feb;262(1):87-91. doi: 10.1007/s00406-011-0217-3. Epub 2011 May 12.

DOI:10.1007/s00406-011-0217-3
PMID:21562895
Abstract

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulatory technique widely used in research, diagnostics, and neuro-psychiatric therapy. Despite its growing popularity, basic molecular mechanisms underlying the clinical effects of rTMS have remained largely under-researched. Here, we present a human-derived neuronal cell culture system responsive to rTMS effects. SH-SY5Y neuroblastoma cells were differentiated by retinoic acid treatment for 10 days, resulting in a neuronal phenotype characterized by upregulation of neuronal marker proteins and generation of an action potential in response to depolarizing current step injection. Repetitive magnetic stimulation of these cells resulted in increased intracellular cAMP levels and increased phosphorylation of transcription factor CREB. Pretreatment with ketamine (1 μM) potentiated, while pretreatment with lithium (2 mM) attenuated this cellular response to repetitive magnetic stimulation. In conclusion, we introduce here a novel in vitro system responding to rTMS at the level of second messenger signaling. The use of human-derived cells with neuron-like properties will prove useful for further studies on the cellular effects of rTMS.

摘要

重复经颅磁刺激(rTMS)是一种广泛应用于研究、诊断和神经精神治疗的非侵入性神经刺激技术。尽管它越来越受欢迎,但 rTMS 临床效果的基本分子机制在很大程度上仍未得到充分研究。在这里,我们提出了一种对 rTMS 效应有反应的人源性神经元细胞培养系统。通过用视黄酸处理 10 天使 SH-SY5Y 神经母细胞瘤细胞分化,得到具有神经元表型的细胞,其特征为神经元标记蛋白的上调和对去极化电流阶跃注入产生动作电位。对这些细胞进行重复磁刺激会导致细胞内环腺苷酸(cAMP)水平升高,并增加转录因子 CREB 的磷酸化。用氯胺酮(1 μM)预处理会增强这种细胞对重复磁刺激的反应,而用锂(2 mM)预处理会减弱这种反应。总之,我们在这里引入了一种新的体外系统,可在第二信使信号转导水平上对 rTMS 做出反应。使用具有类神经元特性的人源性细胞将有助于进一步研究 rTMS 的细胞效应。

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