人类 TRPV1 是一种用于慢性神经调节的高效致热驱动器。

IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cellular and Molecular Life Sciences Pub Date : 2024-10-25 DOI:10.1007/s00018-024-05475-x
Dmitry I Maltsev, Maxim A Solotenkov, Liana F Mukhametshina, Rostislav A Sokolov, Georgy M Solius, David Jappy, Aleksandra S Tsopina, Ilya V Fedotov, Aleksandr A Lanin, Andrei B Fedotov, Viktoriya G Krut', Yulia G Ermakova, Aleksandr A Moshchenko, Andrei Rozov, Aleksei M Zheltikov, Oleg V Podgorny, Vsevolod V Belousov
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引用次数: 0

摘要

热敏技术是一种基于热敏离子通道的神经调节技术,前景广阔。然而,在其临床应用的道路上,还有许多问题需要解决。首先,为避免在未来的人体应用中出现免疫反应,应将人体离子通道作为热遗传致动器进行研究。其次,应研究在体内脑组织中激活这些通道所需的加热水平,并解决这些温度的细胞毒性问题。第三,必须证明慢性神经调节的可能性和安全性。在这项研究中,我们提出了一个利用热敏性人类离子通道 hTRPV1 进行体内热源神经调控的综合框架。通过将 hTRPV1 靶向表达到小鼠大脑的兴奋性神经元,并用光纤耦合红外激光器在无害温度范围内激活它们,我们不仅诱导了小鼠的神经元发射并刺激了小鼠的运动,还证明了热遗传学可用于重复神经调节而不会造成明显的脑组织损伤。我们的研究结果为在脑科学研究和神经病理学治疗中使用热源神经调制奠定了基础。
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Human TRPV1 is an efficient thermogenetic actuator for chronic neuromodulation.

Thermogenetics is a promising neuromodulation technique based on the use of heat-sensitive ion channels. However, on the way to its clinical application, a number of questions have to be addressed. First, to avoid immune response in future human applications, human ion channels should be studied as thermogenetic actuators. Second, heating levels necessary to activate these channels in vivo in brain tissue should be studied and cytotoxicity of these temperatures addressed. Third, the possibility and safety of chronic neuromodulation has to be demonstrated. In this study, we present a comprehensive framework for thermogenetic neuromodulation in vivo using the thermosensitive human ion channel hTRPV1. By targeting hTRPV1 expression to excitatory neurons of the mouse brain and activating them within a non-harmful temperature range with a fiber-coupled infrared laser, we not only induced neuronal firing and stimulated locomotion in mice, but also demonstrated that thermogenetics can be employed for repeated neuromodulation without causing evident brain tissue injury. Our results lay the foundation for the use of thermogenetic neuromodulation in brain research and therapy of neuropathologies.

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来源期刊
Cellular and Molecular Life Sciences
Cellular and Molecular Life Sciences 生物-生化与分子生物学
CiteScore
13.20
自引率
1.20%
发文量
546
审稿时长
1.0 months
期刊介绍: Journal Name: Cellular and Molecular Life Sciences (CMLS) Location: Basel, Switzerland Focus: Multidisciplinary journal Publishes research articles, reviews, multi-author reviews, and visions & reflections articles Coverage: Latest aspects of biological and biomedical research Areas include: Biochemistry and molecular biology Cell biology Molecular and cellular aspects of biomedicine Neuroscience Pharmacology Immunology Additional Features: Welcomes comments on any article published in CMLS Accepts suggestions for topics to be covered
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