Dexmedetomidine Inhibits Paraventricular Corticotropin-releasing Hormone Neurons that Attenuate Acute Stress-induced Anxiety-like Behavior in Mice.

IF 9.1 1区医学 Q1 ANESTHESIOLOGY

Anesthesiology Pub Date : 2024-06-01 DOI:10.1097/ALN.0000000000004982

Gaolin Qiu, Peng Wang, Jin Rao, Xin Qing, Chenchen Cao, Dijia Wang, Bin Mei, Jiqian Zhang, Hu Liu, Zhilai Yang, Xuesheng Liu

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引用次数: 0

Abstract

Background: Dexmedetomidine has repeatedly shown to improve anxiety, but the precise neural mechanisms underlying this effect remain incompletely understood. This study aims to explore the role of corticotropin-releasing hormone-producing hypothalamic paraventricular nucleus (CRHPVN) neurons in mediating the anxiolytic effects of dexmedetomidine.

Methods: A social defeat stress mouse model was used to evaluate the anxiolytic effects induced by dexmedetomidine through the elevated plus maze, open-field test, and measurement of serum stress hormone levels. In vivo Ca2+ signal fiber photometry and ex vivo patch-clamp recordings were used to determine the excitability of CRHPVN neurons and investigate the specific mechanism involved. CRHPVN neuron modulation was achieved through chemogenetic activation or inhibition.

Results: Compared with saline, dexmedetomidine (40 µg/kg) alleviated anxiety-like behaviors. Additionally, dexmedetomidine reduced CRHPVN neuronal excitability. Chemogenetic activation of CRHPVN neurons decreased the time spent in the open arms of the elevated plus maze and in the central area of the open-field test. Conversely, chemogenetic inhibition of CRHPVN neurons had the opposite effect. Moreover, the suppressive impact of dexmedetomidine on CRHPVN neurons was attenuated by the α2-receptor antagonist yohimbine.

Conclusions: The results indicate that the anxiety-like effects of dexmedetomidine are mediated via α2-adrenergic receptor-triggered inhibition of CRHPVN neuronal excitability in the hypothalamus.

Editor’s perspective:

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右美托咪定可抑制脑室旁促肾上腺皮质激素释放激素神经元，从而减轻急性应激诱发的小鼠焦虑样行为。

背景：右美托咪定多次被证明能改善焦虑，但这种效应的确切神经机制仍不完全清楚。在此，我们旨在探索促肾上腺皮质激素释放激素下丘脑室旁神经元（CRHPVN）在介导右美托咪定抗焦虑作用中的作用：方法：采用社会挫败应激小鼠模型，通过高架加迷宫、开放场试验和血清应激激素水平的测定，评估右美托咪定诱导的抗焦虑作用。利用体内Ca2+信号纤维光度计和体外膜片钳记录来确定CRHPVN神经元的兴奋性，并研究其中的具体机制。CRHPVN神经元调节是通过化学基因激活或抑制实现的：结果：与生理盐水相比，右美托咪定（40 µg/kg）可减轻焦虑样行为。此外，右美托咪定还能降低CRHPVN神经元的兴奋性。CRHPVN神经元的化学激活减少了在高架加迷宫的开放臂和开阔地测试的中心区域所花费的时间。相反，对CRHPVN神经元进行化学抑制则会产生相反的效果。此外，右美托咪定对α2受体拮抗剂育亨宾对CRHPVN神经元的抑制作用也有所减弱：我们的研究结果表明，右美托咪定的焦虑样效应是通过α2肾上腺素能受体触发的下丘脑CRHPVN神经元兴奋性抑制作用介导的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anesthesiology 医学-麻醉学

CiteScore

10.40

自引率

5.70%

发文量

542

审稿时长

3-6 weeks

期刊介绍： With its establishment in 1940, Anesthesiology has emerged as a prominent leader in the field of anesthesiology, encompassing perioperative, critical care, and pain medicine. As the esteemed journal of the American Society of Anesthesiologists, Anesthesiology operates independently with full editorial freedom. Its distinguished Editorial Board, comprising renowned professionals from across the globe, drives the advancement of the specialty by presenting innovative research through immediate open access to select articles and granting free access to all published articles after a six-month period. Furthermore, Anesthesiology actively promotes groundbreaking studies through an influential press release program. The journal's unwavering commitment lies in the dissemination of exemplary work that enhances clinical practice and revolutionizes the practice of medicine within our discipline.