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星形胶质细胞分泌表型的光遗传学和化学遗传学调控

Optogenetic and chemogenetic modulation of astroglial secretory phenotype.

作者信息

Salmina Alla B, Gorina Yana V, Erofeev Alexander I, Balaban Pavel M, Bezprozvanny Ilya B, Vlasova Olga L

机构信息

Laboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia.

Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russia.

出版信息

Rev Neurosci. 2021 Feb 8;32(5):459-479. doi: 10.1515/revneuro-2020-0119. Print 2021 Jul 27.

Abstract

Astrocytes play a major role in brain function and alterations in astrocyte function that contribute to the pathogenesis of many brain disorders. The astrocytes are attractive cellular targets for neuroprotection and brain tissue regeneration. Development of novel approaches to monitor and to control astroglial function is of great importance for further progress in basic neurobiology and in clinical neurology, as well as psychiatry. Recently developed advanced optogenetic and chemogenetic techniques enable precise stimulation of astrocytes and , which can be achieved by the expression of light-sensitive channels and receptors, or by expression of receptors exclusively activated by designer drugs. Optogenetic stimulation of astrocytes leads to dramatic changes in intracellular calcium concentrations and causes the release of gliotransmitters. Optogenetic and chemogenetic protocols for astrocyte activation aid in extracting novel information regarding the function of brain's neurovascular unit. This review summarizes current data obtained by this approach and discusses a potential mechanistic connection between astrocyte stimulation and changes in brain physiology.

摘要

星形胶质细胞在脑功能中发挥着重要作用,其功能改变会导致许多脑部疾病的发病机制。星形胶质细胞是神经保护和脑组织再生的有吸引力的细胞靶点。开发监测和控制星形胶质细胞功能的新方法对于基础神经生物学、临床神经病学以及精神病学的进一步发展至关重要。最近开发的先进光遗传学和化学遗传学技术能够精确刺激星形胶质细胞,这可以通过表达光敏通道和受体,或通过表达仅由设计药物激活的受体来实现。对星形胶质细胞的光遗传学刺激会导致细胞内钙浓度发生显著变化,并引起神经递质的释放。用于星形胶质细胞激活的光遗传学和化学遗传学方案有助于提取有关脑微血管单元功能的新信息。本综述总结了通过这种方法获得的当前数据,并讨论了星形胶质细胞刺激与脑生理变化之间潜在的机制联系。

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