Vagal nerve TRPV3 regulates sedative-mediated appeasement
Abstract
Aromatic essential oils (EOs) exhibit anxiolytic properties, yet their neural and molecular mechanisms remain to be understood. Here, we found that citronellal, an EO derived from lemongrass, alleviates stress-related anxiety by modulating vagal tone. We identified transient receptor potential vanilloid 3 (TRPV3) channel in nodose ganglion (NG) as the molecular target of citronellal. TRPV3 was also observed to mediate the antistress effects of the inhaled anesthetic sevoflurane. Both sedatives attenuated acute restraint stress-induced hyperactivity of heart and breath rates via glutamatergic neurotransmission along NG-to-caudal nucleus tractus solitarius (cNTS) pathway. This effect was abolished by surgical vagotomy, Trpv3 −/− , or NG-specific Trpv3 knockdown. Cryo-EM structural analysis revealed that sevoflurane occupies a pore-proximal fenestration site, while citronellal binds to the vanilloid site. Re-expression of wild-type TRPV3, but not loss-of-function TRPV3 mutants TRPV3(A560L) or TRPV3(V662A), in Trpv3 −/− NG neurons restored the mouse’s response to both sedatives, thereby modulating heart and respiratory rates. Together, these findings establish peripheral TRPV3 as a multisensory ligand-gated node for vagal modulation of stress responses, and help instruct pathway-specific anxiolytics.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (20)
Peiyu Wang
State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan University
Jinpiao Zhu
Department of Anesthesiology, Zhongnan Hospital, Wuhan University
Xuteng Lu
State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan University
Chang Chen
Bomin Gao
State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan University
Wanjiang Tao
Department of Anesthesiology, Zhongnan Hospital, Wuhan University
Keyu Xia
State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan University
Yang Song
Sorbonne Université, CNRS, Laboratoire de Chimie de la Matière Condensée de Paris (CMCP), 4 place Jussieu, F-75005 Paris, France
Qiong Shi
State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan University
Hongcun Gai
State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan University
Panhao Xiao
State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan University
Feng Liu
Peiyuan Pang
State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan University
Yang Li
Xiaoyi Mo
Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University
Xiao-Dong Wang
Chang Xie
Department of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine
Dongdong Li
Key Laboratory for Ultrafine Materials of Ministry of Education, Shanghai Engineering Research Center of Hierarchical Nanomaterials, School of Materials Science and Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China
Zongze Zhang
Key Laboratory of Colloid and Interface Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering
Jing Yao