Vagal nerve TRPV3 regulates sedative-mediated appeasement

Area of Science:

• Neuroscience
• Pharmacology
• Molecular Biology

Background:

• Aromatic essential oils (EOs) show anxiolytic potential, but their mechanisms are unclear.
• Understanding the neural pathways of stress and anxiety relief is crucial for developing effective treatments.

Purpose of the Study:

• To elucidate the neural and molecular mechanisms by which citronellal, an essential oil component, alleviates anxiety.
• To identify the molecular targets of citronellal and sevoflurane in stress response modulation.

Main Methods:

• Investigated citronellal's effects on stress-related anxiety in a mouse model.
• Utilized genetic manipulation (Trpv3 knockout and knockdown) and surgical vagotomy.
• Performed cryo-electron microscopy (Cryo-EM) for structural analysis of TRPV3 channel interactions.
• Assessed physiological responses (heart and respiratory rates) and neuronal activity.

Main Results:

• Citronellal alleviates stress-induced anxiety by modulating vagal tone through the TRPV3 channel in the nodose ganglion (NG).
• Sevoflurane shares TRPV3 as a molecular target, with both agents acting via glutamatergic neurotransmission along the NG-to-cNTS pathway.
• Cryo-EM revealed distinct binding sites for citronellal (vanilloid site) and sevoflurane (pore-proximal fenestration) on TRPV3.
• Functional TRPV3 channels in NG neurons are essential for mediating the anxiolytic and anti-stress effects.

Conclusions:

• Peripheral TRPV3 acts as a critical molecular target for both natural compounds (citronellal) and anesthetics (sevoflurane) in regulating stress responses.
• The findings highlight the vagal pathway involving TRPV3 as a potential target for developing novel anxiolytics.