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星形胶质细胞的光遗传学调控:能否用于治疗与星形胶质细胞相关的癫痫?

Optogenetic control of astrocytes: is it possible to treat astrocyte-related epilepsy?

作者信息

Ji Zhi-Gang, Wang Hongxia

机构信息

The Departments of Neurology, Baylor College of Medicine, Houston, TX, United States.

The Departments of Neuroscience, Baylor College of Medicine, Houston, TX, United States.

出版信息

Brain Res Bull. 2015 Jan;110:20-5. doi: 10.1016/j.brainresbull.2014.10.013. Epub 2014 Nov 6.

Abstract

Epilepsy is a neurological disorder that affects around 1% of the population worldwide. The two main therapies, pharmacology and the electrical stimulation, both have some shortcomings. For instance, pharmacological therapy is frequently accompanied by side effects, and current anticonvulsive drugs fail to be effective to around a third of patients. These patients could suffer astrocyte-related epilepsy, as increasing evidence indicates that dysfunctions of astrocytes can result in epilepsy. However, epilepsy drugs that affect astrocytes are not available currently. Although electrical stimulation has benefited many patients, the electrode stimulates unselective neurons or circuits. All these need to develop new strategies for improving the life of the patients. As channelrhodopsins (ChRs) were discovered, a novel method referred to as "optogenetics" was developed. It has advantages over electrical stimulation of being less-invasiveness and allowing spatiotemporally stimulation. Recently, a number of experiments have explored the treatments for epilepsy with optogenetic control of neurons. Here, we discuss the possibility that an optogenetic approach could be used to control the release of gliotransmitters and improve astrocyte function such as glutamate and K(+) uptake, and thereby offer a potential strategy to investigate and treat astrocyte-related epilepsy.

摘要

癫痫是一种影响全球约1%人口的神经系统疾病。两种主要治疗方法,即药物治疗和电刺激,都存在一些缺点。例如,药物治疗常常伴有副作用,而且目前的抗惊厥药物对约三分之一的患者无效。这些患者可能患有与星形胶质细胞相关的癫痫,因为越来越多的证据表明星形胶质细胞功能障碍会导致癫痫。然而,目前尚无影响星形胶质细胞的癫痫药物。尽管电刺激使许多患者受益,但电极会无选择性地刺激神经元或神经回路。所有这些都需要开发新的策略来改善患者的生活。随着通道视紫红质(ChRs)的发现,一种被称为“光遗传学”的新方法应运而生。它比电刺激具有侵入性小和能进行时空刺激的优势。最近,一些实验探索了用光遗传学控制神经元来治疗癫痫。在此,我们讨论光遗传学方法可用于控制神经胶质递质释放并改善星形胶质细胞功能(如谷氨酸和钾离子摄取)的可能性,从而为研究和治疗与星形胶质细胞相关的癫痫提供一种潜在策略。

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