癫痫与光遗传学:癫痫发作能被光控制吗?

Epilepsy and optogenetics: can seizures be controlled by light?

作者信息

Tønnesen Jan, Kokaia Merab

机构信息

Laboratory of Neuronal Excitability, Achucarro Basque Center for Neuroscience, Sede Building, Barrio Sarriena, s/n, 48940 Leioa, Spain

Department of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Barrio Sarriena, s/n, 48940 Leioa, Spain.

出版信息

Clin Sci (Lond). 2017 Jun 30;131(14):1605-1616. doi: 10.1042/CS20160492. Print 2017 Jul 15.

Abstract

Over the past decade, 'optogenetics' has been consolidated as a game-changing tool in the neuroscience field, by allowing optical control of neuronal activity with high cell-type specificity. The ability to activate or inhibit targeted neurons at millisecond resolution not only offers an investigative tool, but potentially also provides a therapeutic intervention strategy for acute correction of aberrant neuronal activity. As efficient therapeutic tools are in short supply for neurological disorders, optogenetic technology has therefore spurred considerable enthusiasm and fostered a new wave of translational studies in neuroscience. Epilepsy is among the disorders that have been widely explored. Partial epilepsies are characterized by seizures arising from excessive excitatory neuronal activity that emerges from a focal area. Based on the constricted seizure focus, it appears feasible to intercept partial seizures by acutely shutting down excitatory neurons by means of optogenetics. The availability of both inhibitory and excitatory optogenetic probes, along with the available targeting strategies for respective excitatory or inhibitory neurons, allows multiple conceivable scenarios for controlling abnormal circuit activity. Several such scenarios have been explored in the settings of experimental epilepsy and have provided encouraging translational findings and revealed interesting and unexpected new aspects of epileptogenesis. However, it has also emerged that considerable challenges persist before clinical translation becomes feasible. This review provides a general introduction to optogenetics, and an overview of findings that are relevant for understanding how optogenetics may be utilized therapeutically as a highly innovative treatment for epilepsy.

摘要

在过去十年中,“光遗传学”已巩固成为神经科学领域一项改变游戏规则的工具,它能够以高度的细胞类型特异性对神经元活动进行光学控制。以毫秒级分辨率激活或抑制靶向神经元的能力不仅提供了一种研究工具,而且还可能为急性纠正异常神经元活动提供一种治疗干预策略。由于神经系统疾病的有效治疗工具短缺,光遗传学技术因此激发了人们相当大的热情,并在神经科学领域催生了新一轮的转化研究浪潮。癫痫是已被广泛探索的疾病之一。部分性癫痫的特征是由局灶性区域出现的过度兴奋性神经元活动引起的癫痫发作。基于狭窄的癫痫发作灶,通过光遗传学急性关闭兴奋性神经元来拦截部分性癫痫发作似乎是可行的。抑制性和兴奋性光遗传学探针的可用性,以及针对各自兴奋性或抑制性神经元的可用靶向策略,为控制异常电路活动提供了多种可想象的方案。在实验性癫痫的背景下已经探索了几种这样的方案,它们提供了令人鼓舞的转化研究结果,并揭示了癫痫发生的有趣且意想不到的新方面。然而,也已经出现,在临床转化变得可行之前,仍然存在相当大的挑战。本综述对光遗传学进行了一般性介绍,并概述了与理解如何将光遗传学作为一种极具创新性的癫痫治疗方法进行治疗相关的研究结果。

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