Electrical Stimulation by an Organic Transistor Architecture Induces Calcium Signaling in Nonexcitable Brain Cells
Electrical Stimulation by an Organic Transistor Architecture Induces Calcium Signaling in Nonexcitable Brain Cells
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DOI：
10.1002/adhm.201801139
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发表时间：
2019-02-07
影响因子：
10
通讯作者：
Benfenati, Valentina
中科院分区：
文献类型：
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作者：
Borrachero-Conejo, Ana Isabel;Saracino, Emanuela;Benfenati, Valentina
有机生物电子学具有巨大的潜力，可以产生用于研究大脑功能和治疗大脑病理的接口和设备。在这种情况下，需要越来越多的努力来开发用于监测和刺激非兴奋性脑细胞（称为星形胶质细胞）的技术。星形胶质细胞钙信号在大脑的生理和病理生理中起着关键作用。在这里，使用透明的有机细胞刺激和传感晶体管（O-CST）架构，制造与N，N '-双十三烷基苝-3，4，9，10-四羧酸二酰亚胺（P13），引发和监测细胞内钙浓度（[Ca 2 +]（i））在原代大鼠新皮层星形胶质细胞中的证明。O-CST的透明性允许进行钙成像实验，表明星形胶质细胞的细胞外电刺激诱导[Ca 2 +]（i）的急剧增加。药理学研究表明，瞬时受体电位（TRP）超家族是[Ca 2 +]（i）增加的关键介质。实验和计算分析表明，[Ca 2 +]（i）响应是由O-CST器件结构实现的。值得注意的是，胞外场的应用诱导细胞体积轻微但显著的增加。总的来说，O-CST能够选择性地唤起星形胶质细胞[Ca 2 +]（i），为开发有机生物电子器件作为神经胶质界面以激发和控制非神经元脑细胞的生理学铺平了道路。
Organic bioelectronics have a huge potential to generate interfaces and devices for the study of brain functions and for the therapy of brain pathologies. In this context, increasing efforts are needed to develop technologies for monitoring and stimulation of nonexcitable brain cells, called astrocytes. Astroglial calcium signaling plays, indeed, a pivotal role in the physiology and pathophysiology of the brain. Here, the use of transparent organic cell stimulating and sensing transistor (O-CST) architecture, fabricated with N,N'-ditridecylperylene-3,4,9,10-tetracarboxylic diimide (P13), to elicit and monitor intracellular calcium concentration ([Ca2+](i)) in primary rat neocortical astrocytes is demonstrated. The transparency of O-CST allows performing calcium imaging experiments, showing that extracellular electrical stimulation of astrocytes induces a drastic increase in [Ca2+](i). Pharmacological studies indicate that transient receptor potential (TRP) superfamily are critical mediators of the [Ca2+](i) increase. Experimental and computational analyses show that [Ca2+](i) response is enabled by the O-CST device architecture. Noteworthy, the extracellular field application induces a slight but significant increase in the cell volume. Collectively, it is shown that the O-CST is capable of selectively evoking astrocytes [Ca2+](i), paving the way to the development of organic bioelectronic devices as glial interfaces to excite and control physiology of non-neuronal brain cells.