Experimental and Regenerative Neuroscience, School of Biological Sciences, The University of Western Australia, Nedlands, WA, 6009, Australia; Perron Institute for Neurological and Translational Science, Nedlands, WA, 6009, Australia.
Experimental and Regenerative Neuroscience, School of Biological Sciences, The University of Western Australia, Nedlands, WA, 6009, Australia; Perron Institute for Neurological and Translational Science, Nedlands, WA, 6009, Australia.
Brain Stimul. 2021 Jan-Feb;14(1):183-191. doi: 10.1016/j.brs.2020.12.007. Epub 2020 Dec 24.
Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive brain stimulation frequently used to induce neuroplasticity in the brain. Even at low intensities, rTMS has been shown to modulate aspects of neuronal plasticity such as motor learning and structural reorganisation of neural tissue. However, the impact of low intensity rTMS on glial cells such as astrocytes remains largely unknown. This study investigated changes in RNA (qPCR array: 125 selected genes) and protein levels (immunofluorescence) in cultured mouse astrocytes following a single session of low intensity repetitive magnetic stimulation (LI-rMS - 18 mT). Purified neonatal cortical astrocyte cultures were stimulated with either 1Hz (600 pulses), 10Hz (600 or 6000 pulses) or sham (0 pulses) LI-rMS, followed by RNA extraction at 5 h post-stimulation, or fixation at either 5 or 24-h post-stimulation. LI-rMS resulted in a two-to-four-fold downregulation of mRNA transcripts related to calcium signalling (Stim1 and Orai3), inflammatory molecules (Icam1) and neural plasticity (Ncam1). 10Hz reduced expression of Stim1, Orai3, Kcnmb4, and Ncam1 mRNA, whereas 1Hz reduced expression of Icam1 mRNA and signalling-related genes. Protein levels followed a similar pattern for 10Hz rMS, with a significant reduction of STIM1, ORAI3, KCNMB4, and NCAM1 protein compared to sham, but 1Hz increased STIM1 and ORAI3 protein levels relative to sham. These findings demonstrate the ability of 1Hz and 10Hz LI-rMS to modulate specific aspects of astrocytic phenotype, potentially contributing to the known effects of low intensity rTMS on excitability and neuroplasticity.
重复经颅磁刺激（rTMS）是一种非侵入性脑刺激形式，常用于诱导大脑的神经可塑性。即使在低强度下，rTMS 已被证明可以调节神经元可塑性的各个方面，例如运动学习和神经组织的结构重组。然而，低强度 rTMS 对星形胶质细胞等神经胶质细胞的影响在很大程度上仍然未知。本研究调查了单次低强度重复磁刺激（LI-rMS-18 mT）后培养的小鼠星形胶质细胞中的 RNA（qPCR 阵列：125 个选定基因）和蛋白质水平（免疫荧光）的变化。用 1Hz（600 个脉冲）、10Hz（600 或 6000 个脉冲）或假刺激（0 个脉冲）LI-rMS 刺激纯化的新生皮质星形胶质细胞培养物，然后在刺激后 5 小时提取 RNA，或在刺激后 5 或 24 小时固定。LI-rMS 导致与钙信号（Stim1 和 Orai3）、炎症分子（Icam1）和神经可塑性（Ncam1）相关的 mRNA 转录物下调 2 到 4 倍。10Hz 降低了 Stim1、Orai3、Kcnmb4 和 Ncam1 mRNA 的表达，而 1Hz 降低了 Icam1 mRNA 和信号相关基因的表达。10Hz rMS 的蛋白质水平也呈现出类似的模式，与假刺激相比，STIM1、ORAI3、KCNMB4 和 NCAM1 蛋白显著减少，但 1Hz 相对于假刺激增加了 STIM1 和 ORAI3 蛋白水平。这些发现表明 1Hz 和 10Hz LI-rMS 能够调节星形胶质细胞表型的特定方面，这可能有助于解释低强度 rTMS 对兴奋性和神经可塑性的已知影响。
