The activation of GABAergic neurons in the hypothalamic tuberomammillary nucleus attenuates sevoflurane and propofol-induced anesthesia in mice

Jing Liu; Xiao Liu; Wen-Yu Zhou; Jun Gan; Jie Wang; Qi Zhang; Jun-Liang Li; Zhong-Shan Shen; Yue-Ying Zhang; Qiong-Yao Tang; Zhe Zhang

doi:10.3389/fphar.2023.1153735

The activation of GABAergic neurons in the hypothalamic tuberomammillary nucleus attenuates sevoflurane and propofol-induced anesthesia in mice

Front Pharmacol. 2023 Jun 22:14:1153735. doi: 10.3389/fphar.2023.1153735. eCollection 2023.

Authors

Jing Liu^{1

2

3

4}, Xiao Liu^{1

2

3}, Wen-Yu Zhou^{1

2

3}, Jun Gan^{1

2

3}, Jie Wang^{1

2

3}, Qi Zhang^{1

2

3}, Jun-Liang Li^{1

2

3}, Zhong-Shan Shen^{1

2

3}, Yue-Ying Zhang⁵, Qiong-Yao Tang^{1

2

3}, Zhe Zhang^{1

2

3}

Affiliations

¹ Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
² Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
³ NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu, China.
⁴ Department of Cell Biology and Neurobiology, Life Sciences College, Xuzhou Medical University, Xuzhou, Jiangsu, China.
⁵ Department of Anesthesia, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

Abstract

Background: The histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN) have been suggested to play a vital role in maintaining a rising state. But the neuronal types of the TMN are in debate and the role of GABAergic neurons remains unclear. Methods: In the present study, we examined the role of TMN GABAergic neurons in general anesthesia using chemogenetics and optogenetics strategies to regulate the activity of TMN GABAergic neurons. Results: The results indicated that either chemogenetic or optogenetic activation of TMN GABAergic neurons in mice decreased the effect of sevoflurane and propofol anesthesia. In contrast, inhibition of the TMN GABAergic neurons facilitates the sevoflurane anesthesia effect. Conclusion: Our results suggest that the activity of TMN GABAergic neurons produces an anti-anesthesia effect in loss of consciousness and analgesia.

Keywords: anesthesia; gabaergic neurons; hypothalamic tuberomammillary nucleus; propofol; sevoflurane.

Grants and funding

This work was supported by The Important Project of Natural Science in Colleges and Universities in Jiangsu Province to ZZ (14KJA320002), Jiangsu specially appointed professor to ZZ and Q-YT, Natural Science Foundation of China (NSFC) grant to ZZ (81471314 and 81671090), Natural Science Foundation of Jiangsu Province to ZZ (SBK201502515), Xuzhou Science and Technology Program (KC19036) to ZZ and (KC16H0230) to Q-YT, an NSFC grant to Q-YT (31671212), China Postdoctoral Science Foundation to LJ (2022M712682), Medical research project of Jiangsu Provincial Health Commission to LJ (Grant number: Z2022041), College Students Innovation and entrepreneurship training program of Jiangsu Province to W-YZ (201910313033Z). We also appreciate the grant support from the Priority Academic Program Development of Jiangsu Higher Education Institutions and the Jiangsu Provincial Special Program of Medical Science (BL2014029).