School of Biomedical Engineering, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
J Neural Eng. 2021 Jul 2;18(4). doi: 10.1088/1741-2552/ac0b50.
. Electrical brain stimulation has been used to ameliorate symptoms associated with neurologic and psychiatric disorders. The astrocytic activation and its interaction with neurons may contribute to the therapeutic effects of electrical stimulation. However, how the astrocytic activity is affected by electrical stimulation and its calcium signaling mechanisms remain largely unknown. This study is to explore the influence of electrical stimulus parameters on cellular calcium responses and corresponding calcium signaling mechanisms, with a focus on the heretofore largely overlooked astrocytes.. Usingtwo-photon microscopy in mouse somatosensory cortex, the calcium activity in neurons and astrocytes were recorded.. The cathodal stimulation evoked larger responses in both neurons and astrocytes than anodal stimulation. Both neuronal and astrocytic response profiles exhibited the unimodal frequency dependency, the astrocytes prefer higher frequency stimulation than neurons. Astrocytes need longer pulse width and higher current intensity than neurons to activate. Compared to neurons, the astrocytes were not capable of keeping sustained calcium elevation during prolonged electrical stimulation. The neuronal Cainflux involves postsynaptic effects and direct depolarization. The Casurge of astrocytes has a neuronal origin, the noradrenergic and glutamatergic signaling act synergistically to induce astrocytic activity.. The astrocytic activity can be regulated by manipulating stimulus parameters and its calcium activation should be fully considered when interpreting the mechanisms of action of electrical neuromodulation. This study brings considerable benefits in the application of electrical stimulation and provides useful insights into cortical signal transduction, which contributes to the understanding of mechanisms underlying the therapeutic efficacy of electrical stimulation for neurorehabilitation applications.
电脑刺激已被用于改善与神经和精神疾病相关的症状。星形胶质细胞的激活及其与神经元的相互作用可能有助于电刺激的治疗效果。然而，电刺激如何影响星形胶质细胞活性及其钙信号机制在很大程度上仍不清楚。本研究旨在探索电刺激参数对细胞钙反应的影响及其相应的钙信号机制，重点关注迄今在很大程度上被忽视的星形胶质细胞。
在小鼠体感皮层中使用双光子显微镜，记录神经元和星形胶质细胞中的钙活性。
阴极刺激比阳极刺激在神经元和星形胶质细胞中引起更大的反应。神经元和星形胶质细胞的反应谱均表现出单峰频率依赖性，星形胶质细胞比神经元更喜欢高频刺激。与神经元相比，星形胶质细胞在长时间电刺激期间无法保持持续的钙升高。神经元的钙内流涉及突触后效应和直接去极化。星形胶质细胞的钙激增具有神经元起源，去甲肾上腺素能和谷氨酸能信号协同作用诱导星形胶质细胞活性。
星形胶质细胞的活性可以通过操纵刺激参数来调节，在解释电神经调节作用机制时，应充分考虑其钙激活。本研究在电刺激的应用中带来了相当大的好处，并为皮层信号转导提供了有用的见解，有助于理解电刺激治疗神经康复应用的疗效机制。
