Direct current stimulation modulates gene expression in isolated astrocytes with implications for glia-mediated plasticity.

Direct current stimulation modulates gene expression in isolated astrocytes with implications for glia-mediated plasticity.
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直流刺激调节孤立星形胶质细胞中的基因表达,对胶质介导的可塑性有影响。

DOI:
10.1038/s41598-022-22394-8
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发表时间:
2022-10-26
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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虽然经颅直流电刺激 (tDCS) 在脑疾病和认知方面的应用多种多样,但它们依赖于刺激后大脑功能的变化。 DCS 导致大脑可塑性的细胞机制已被研究,但星形胶质细胞的作用仍未得到解决。我们之前预测,在 tDCS 期间,电流集中穿过血脑屏障。这将增加形成血管的内皮细胞(EC)和包裹血管的星形胶质细胞的暴露。本研究的目的是研究 tDCS 对星形胶质细胞或 EC 基因表达的影响。 DCS(0.1 或 1 mA,10 分钟)应用于小鼠脑 EC 或人星形胶质细胞的单层。使用 RT-qPCR 测量一组神经活性基因的基因表达。 DCS 后立即或 1 小时评估表达。因为我们之前表明 DCS 可以产生已知会影响 EC 和星形胶质细胞功能的电渗流和流体剪切应力,所以我们比较了三种干预措施:仅穿过单层的压力驱动流、压力驱动流加 DCS 以及单独的 DCS 并阻塞流。我们证明 DCS 可以直接调节星形胶质细胞中的基因表达(特别是 FOS 和 BDNF),独立于压力驱动流基因表达,但与压力驱动流基因表达具有协同作用。在 EC 中,压力驱动的流动激活基因表达,但没有证据表明 DCS 进一步发挥作用。在 EC 中,单独使用 DCS 会产生混合效应,包括 FGF9 上调和 NTF3 下调。我们提出了一种基于神经胶质介导可塑性的 tDCS 新辅助机制。
While the applications of transcranial direct current stimulation (tDCS) across brain disease and cognition are diverse, they rely on changes in brain function outlasting stimulation. The cellular mechanisms of DCS leading to brain plasticity have been studied, but the role of astrocytes remains unaddressed. We previously predicted that during tDCS current is concentrated across the blood brain-barrier. This will amplify exposure of endothelial cells (ECs) that form blood vessels and of astrocytes that wrap around them. The objective of this study was to investigate the effect of tDCS on the gene expression by astrocytes or ECs. DCS (0.1 or 1 mA, 10 min) was applied to monolayers of mouse brain ECs or human astrocytes. Gene expression of a set of neuroactive genes were measured using RT-qPCR. Expression was assessed immediately or 1 h after DCS. Because we previously showed that DCS can produce electroosmotic flow and fluid shear stress known to influence EC and astrocyte function, we compared three interventions: pressure-driven flow across the monolayer alone, pressure-driven flow plus DCS, and DCS alone with flow blocked. We show that DCS can directly modulate gene expression in astrocytes (notably FOS and BDNF), independent of but synergistic with pressure-driven flow gene expression. In ECs, pressure-driven flow activates genes expression with no evidence of further contribution from DCS. In ECs, DCS alone produced mixed effects including an upregulation of FGF9 and downregulation of NTF3. We propose a new adjunct mechanism for tDCS based on glial meditated plasticity.
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