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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Publication Details

Journal
Cellular and Molecular Life Sciences
Published
2024-10-25
DOI
https://doi.org/10.1007/s00018-024-05475-x
Citations
5
Primary Topic
Heart Rate Variability and Autonomic Control
Type
article
Field-Weighted Citation Impact
2.01

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article

Human TRPV1 is an efficient thermogenetic actuator for chronic neuromodulation

Yulia G. Ermakova, A. А. Lanin, Oleg V. Podgorny, Andrei V. Rozov et al.
5 citations
Cellular and Molecular Life Sciences
Heart Rate Variability and Autonomic Control
2.01
article

Human TRPV1 is an efficient thermogenetic actuator for chronic neuromodulation

Yulia G. Ermakova, A. А. Lanin, Oleg V. Podgorny, Andrei V. Rozov, Liana F. Mukhametshina, Viktoriya G. Krut’, Aleksandr A. Moshchenko, Vsevolod Vadimovich Belousov, Rostislav A. Sokolov, Maxim A. Solotenkov, David Jappy, А. М. Желтиков, Dmitry I. Maltsev, Aleksandra S. Tsopina, Andrei B. Fedotov, Ilya V. Fedotov, Georgy M. Solius
article en
5 citations

Abstract

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.

Cellular and Molecular Life SciencesVol. 81(1)
Lomonosov Moscow State University (RU), Kazan Federal University (RU), Pirogov Russian National Research Medical University (RU), Institute of Bioorganic Chemistry (RU), European Molecular Biology Laboratory (DE), Moscow State University (TJ), Federal Medical-Biological Agency (RU), N. I. Lobachevsky State University of Nizhny Novgorod (RU), Thermo Fisher Scientific (Norway) (NO)
Russian Science Foundation
Openalex Percentile: Top 12%
Heart Rate Variability and Autonomic Control
2.01
DOIOpen Access PDFOpenAlex
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