使用平面微电极阵列检测星形胶质细胞慢振荡活动及对致痫化合物的反应。
Detection of astrocytic slow oscillatory activity and response to seizurogenic compounds using planar microelectrode array.
作者信息
Kuroda Taeko, Matsuda Naoki, Ishibashi Yuto, Suzuki Ikuro
机构信息
Department of Electronics, Graduate School of Engineering, Tohoku Institute of Technology, Sendai, Japan.
出版信息
Front Neurosci. 2023 Jan 10;16:1050150. doi: 10.3389/fnins.2022.1050150. eCollection 2022.
Since the development of the planar microelectrode array (MEA), it has become popular to evaluate compounds based on the electrical activity of rodent and human induced pluripotent stem cell (iPSC)-derived neurons. However, there are no reports recording spontaneous human astrocyte activity from astrocyte-only culture sample by MEA. It is becoming clear that astrocytes play an important role in various neurological diseases, and astrocytes are expected to be excellent candidates for targeted therapeutics for the treatment of neurological diseases. Therefore, measuring astrocyte activity is very important for drug development for astrocytes. Recently, astrocyte activity has been found to be reflected in the low-frequency band < 1 Hz, which is much lower than the frequency band for recording neural activity. Here, we separated the signals obtained from human primary astrocytes cultured on MEA into seven frequency bands and successfully recorded the extracellular electrical activity of human astrocytes. The slow waveforms of spontaneous astrocyte activity were observed most clearly in direct current potentials < 1 Hz. We established nine parameters to assess astrocyte activity and evaluated five seizurogenic drug responses in human primary astrocytes and human iPSC-derived astrocytes. Astrocytes demonstrated the most significant dose-dependent changes in pilocarpine. Furthermore, in a principal component analysis using those parameter sets, the drug responses to each seizurogenic compound were separated. In this paper, we report the spontaneous electrical activity measurement of astrocytes alone using MEA for the first time and propose that the MEA measurement focusing on the low-frequency band could be useful as one of the methods to assess drug response .
自从平面微电极阵列(MEA)问世以来,基于啮齿动物和人类诱导多能干细胞(iPSC)衍生神经元的电活动来评估化合物已变得很普遍。然而,尚无通过MEA从仅含星形胶质细胞的培养样本中记录人类星形胶质细胞自发活动的报道。越来越明显的是,星形胶质细胞在各种神经系统疾病中发挥着重要作用,并且星形胶质细胞有望成为治疗神经系统疾病的靶向治疗的优秀候选者。因此,测量星形胶质细胞的活性对于开发针对星形胶质细胞的药物非常重要。最近,已发现星形胶质细胞的活性反映在低于1 Hz的低频带中,这比记录神经活动的频带低得多。在这里,我们将从培养在MEA上的人类原代星形胶质细胞获得的信号分离为七个频带,并成功记录了人类星形胶质细胞的细胞外电活动。在<1 Hz的直流电位中,最清楚地观察到了自发星形胶质细胞活动的慢波形。我们建立了九个参数来评估星形胶质细胞的活性,并评估了人类原代星形胶质细胞和人类iPSC衍生的星形胶质细胞对五种致痫药物的反应。星形胶质细胞在毛果芸香碱中表现出最显著的剂量依赖性变化。此外,在使用这些参数集的主成分分析中,对每种致痫化合物的药物反应被分开。在本文中,我们首次报告了使用MEA单独测量星形胶质细胞的自发电活动,并提出专注于低频带的MEA测量可用作评估药物反应的方法之一。