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通过激活位于蓝斑去甲肾上腺素能神经元中的褪黑素MT受体选择性增强雄性大鼠的快速眼动睡眠。

Selective Enhancement of REM Sleep in Male Rats through Activation of Melatonin MT Receptors Located in the Locus Ceruleus Norepinephrine Neurons.

作者信息

López-Canul Martha, He Qianzi, Sasson Tania, Ettaoussi Mohamed, Gregorio Danilo De, Ochoa-Sanchez Rafael, Catoire Helene, Posa Luca, Rouleau Guy, Beaulieu Jean Martin, Comai Stefano, Gobbi Gabriella

机构信息

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada.

IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.

出版信息

J Neurosci. 2024 Jul 17;44(29):e0914232024. doi: 10.1523/JNEUROSCI.0914-23.2024.

DOI:10.1523/JNEUROSCI.0914-23.2024
PMID:38744530
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11255427/
Abstract

Sleep disorders affect millions of people around the world and have a high comorbidity with psychiatric disorders. While current hypnotics mostly increase non-rapid eye movement sleep (NREMS), drugs acting selectively on enhancing rapid eye movement sleep (REMS) are lacking. This polysomnographic study in male rats showed that the first-in-class selective melatonin MT receptor partial agonist UCM871 increases the duration of REMS without affecting that of NREMS. The REMS-promoting effects of UCM871 occurred by inhibiting, in a dose-response manner, the firing activity of the locus ceruleus (LC) norepinephrine (NE) neurons, which express MT receptors. The increase of REMS duration and the inhibition of LC-NE neuronal activity by UCM871 were abolished by MT pharmacological antagonism and by an adeno-associated viral (AAV) vector, which selectively knocked down MT receptors in the LC-NE neurons. In conclusion, MT receptor agonism inhibits LC-NE neurons and triggers REMS, thus representing a novel mechanism and target for REMS disorders and/or psychiatric disorders associated with REMS impairments.

摘要

睡眠障碍影响着全球数百万人，且与精神疾病的共病率很高。虽然目前的催眠药大多能增加非快速眼动睡眠（NREMS），但缺乏选择性作用于增强快速眼动睡眠（REMS）的药物。这项针对雄性大鼠的多导睡眠图研究表明，一流的选择性褪黑素MT受体部分激动剂UCM871增加了快速眼动睡眠的时长，而不影响非快速眼动睡眠的时长。UCM871促进快速眼动睡眠的作用是通过以剂量反应方式抑制表达MT受体的蓝斑（LC）去甲肾上腺素（NE）神经元的放电活动来实现的。MT药理学拮抗作用以及一种腺相关病毒（AAV）载体消除了UCM871对快速眼动睡眠时长的增加作用以及对LC-NE神经元活动的抑制作用，该载体选择性地敲低了LC-NE神经元中的MT受体。总之，MT受体激动作用抑制LC-NE神经元并引发快速眼动睡眠，因此代表了与快速眼动睡眠障碍和/或与快速眼动睡眠受损相关的精神疾病相关的一种新机制和靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/94eb99d01313/jneuro-44-e0914232024-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/d87733f328f1/jneuro-44-e0914232024-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/83a9ad8abbd3/jneuro-44-e0914232024-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/6c0b0cc0dee8/jneuro-44-e0914232024-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/d13353fba0d0/jneuro-44-e0914232024-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/3e4f1339504e/jneuro-44-e0914232024-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/39381c6d23a2/jneuro-44-e0914232024-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/a18f4e64a448/jneuro-44-e0914232024-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/94eb99d01313/jneuro-44-e0914232024-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/d87733f328f1/jneuro-44-e0914232024-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/83a9ad8abbd3/jneuro-44-e0914232024-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/6c0b0cc0dee8/jneuro-44-e0914232024-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/d13353fba0d0/jneuro-44-e0914232024-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/3e4f1339504e/jneuro-44-e0914232024-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/39381c6d23a2/jneuro-44-e0914232024-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/a18f4e64a448/jneuro-44-e0914232024-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34da/11255427/94eb99d01313/jneuro-44-e0914232024-g008.jpg

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Pharmacol Res. 2023 Dec;198:106993. doi: 10.1016/j.phrs.2023.106993. Epub 2023 Nov 14.
2
When the Locus Coeruleus Speaks Up in Sleep: Recent Insights, Emerging Perspectives.蓝斑活跃时的睡眠：最新见解、新兴视角。
Int J Mol Sci. 2022 Apr 30;23(9):5028. doi: 10.3390/ijms23095028.
3
Rapid eye movement sleep behaviour disorder: Past, present, and future.快速眼动睡眠行为障碍：过去、现在和未来。
参数共振脑模型。
Sci Rep. 2024 Oct 21;14(1):24657. doi: 10.1038/s41598-024-76610-8.
J Sleep Res. 2022 Aug;31(4):e13612. doi: 10.1111/jsr.13612. Epub 2022 Apr 25.
4
The Locus Coeruleus- Norepinephrine System in Stress and Arousal: Unraveling Historical, Current, and Future Perspectives.应激与觉醒中的蓝斑-去甲肾上腺素系统：解读历史、现状与未来展望
Front Psychiatry. 2021 Jan 27;11:601519. doi: 10.3389/fpsyt.2020.601519. eCollection 2020.
5
REM sleep promotes experience-dependent dendritic spine elimination in the mouse cortex.快速眼动睡眠促进小鼠大脑皮层中经验依赖性树突棘消除。
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6
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7
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