Geraniol enhances inhibitory inputs to the paraventricular thalamic nucleus and induces sedation in mice

Xu，Ling2; Liu，Ming Zhe3; Yang，Ya Yue4; Wang，Yan2; Hua，Xiao Xiao5; Du，Li Xia4; Zhu，Jian Yu4; Shen，Yang2; Wang，Yan Qing4,6; Zhang，Ling5; Mi，Wen Li4,6; Mu，Di1,2

2022-04-01

10.1016/j.phymed.2022.153965

PHYTOMEDICINE   影响因子和分区

0944-7113

1618-095X

Background: Plant extracts with sedative effects have a long history of clinical use for treating insomnia and epilepsy. Geraniol (GE), a plant-derived acyclic monoterpene, reduces locomotion and prolongs barbiturate-induced anesthesia in rats. However, the mechanisms of GE in sedation remain elusive. Purpose: This study aimed to investigate the mechanisms of GE in sedation in mice. Methods: GE was administered systemically by nebulization and intraperitoneal injection. Open field tests, acute seizure tests, and electroencephalogram (EEG) recordings were performed to examine the sedative effects of GE in mice. The time of loss of the righting reflex and return of the righting reflex were recorded in anesthesia experiments to examine the effect of GE on anesthesia. In vitro c-Fos staining and in vivo fiber photometry recordings were performed to detect the activity change of the paraventricular thalamic nucleus (PVT). Microinjection of GE into PVT and related behavioral tests were performed to confirm that PVT was a critical target for GE. Whole-cell recordings were performed to dissect the effects of GE on PVT neurons via GABA receptors. Molecular docking was performed to examine the interaction between GE and GABA receptor subunits. Results: We found that GE reduced locomotion, relieved acute seizures, altered the EEG, and facilitated general anesthesia in mice. Next, we found that GE decreased c-Fos expression and suppressed the calcium activity in PVT. Microinjection of GE into PVT reduced locomotion and facilitated anesthesia. Furthermore, electrophysiology results showed that GE induced dramatic membrane hyperpolarization and suppressed the activity of PVT neurons, mainly by prolonging spontaneous inhibitory postsynaptic currents and inducing tonic inhibitory currents. Molecular docking results indicated that the β3 subunit might be a potential target for GE. Conclusion: By combined using behavioral tests, immunohistochemistry, calcium recording, and electrophysiology, we systematically revealed that GE inhibits PVT and induces sedation in mice. Essential oils have long been considered part of traditional medicine, and they are playing a critical role in aromatherapy. Since GE has a comparatively ideal safety property and multiple delivery methods, GE has great application potential in aromatherapy. Our study also provides a potential candidate for further development of sedatives and anaesthetics.

GABAA receptors Geraniol Paraventricular thalamic nucleus Sedation Tonic inhibition

SCI

英语

其他

National Natural Science Foundation of China["31900717","81771202"] ; China Association for Science and Technology[2019QNRC001] ; Shanghai Sailing Program[19YF1438700] ; Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function[21DZ2271800]

Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine

Plant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy

WOS:000821698400002

ELSEVIER GMBH

PHARMACOLOGY & TOXICOLOGY

2-s2.0-85124246604

Scopus

1.SUSTech Center for Pain Medicine,School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China
2.Department of Anesthesiology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,201620,China
3.Department of Respiratory,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,510120,China
4.Department of Integrative Medicine and Neurobiology,School of Basic Medical Science,Institutes of Integrative Medicine,Institutes of Brain Science,Medical College,Fudan University,Shanghai,200032,China
5.The First Rehabilitation Hospital of Shanghai,Tongji University School of Medicine,Shanghai,200090,China
6.Shanghai Key Laboratory for Acupuncture Mechanism and Acupoint Function,Fudan University,Shanghai,200433,China

Xu，Ling,Liu，Ming Zhe,Yang，Ya Yue,et al. Geraniol enhances inhibitory inputs to the paraventricular thalamic nucleus and induces sedation in mice[J]. PHYTOMEDICINE,2022,98.

Xu，Ling.,Liu，Ming Zhe.,Yang，Ya Yue.,Wang，Yan.,Hua，Xiao Xiao.,...&Mu，Di.(2022).Geraniol enhances inhibitory inputs to the paraventricular thalamic nucleus and induces sedation in mice.PHYTOMEDICINE,98.

Xu，Ling,et al."Geraniol enhances inhibitory inputs to the paraventricular thalamic nucleus and induces sedation in mice".PHYTOMEDICINE 98(2022).