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钩藤碱对基因敲除小鼠的催眠作用。

Sleep-inducing effect of Rhynchophylline in knockout mice.

作者信息

Ballester Roig Maria Neus, Mongrain Valérie

机构信息

Department of Neuroscience, Université de Montréal, Montréal, QC, Canada.

Center for Advanced Research in Sleep Medicine, Recherche CIUSSS-NIM, Montréal, QC, Canada.

出版信息

Sleep Adv. 2023 Sep 27;4(1):zpad037. doi: 10.1093/sleepadvances/zpad037. eCollection 2023.

DOI:10.1093/sleepadvances/zpad037
PMID:37840649
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10572089/
Abstract

We have recently demonstrated that the alkaloid rhynchophylline (RHY; purified from plants) induces sleep and modifies electrocorticographic (ECoG) activity throughout the 24-h day in a vigilance state-dependent manner in wild-type mice. We here asked whether this alkaloid impacts wake/sleep variables in the absence of the cell adhesion protein EPHA4, via ECoG recording in knockout (KO) mice submitted to the same RHY treatment contemporaneously to the wild-type mice (littermates). We uncover that RHY decreases time spent awake and increases time spent in slow wave sleep in KO mice and alters the 24-h time course of ECoG activity during wakefulness and sleep states. These observations are similar to the reported effects of RHY in wild-type littermate animals, which strongly supports that RHY-driven sleep alterations are not dependent on the presence of EPHA4.

摘要

我们最近证明,生物碱钩藤碱(RHY;从植物中纯化得到)能诱导野生型小鼠睡眠,并以与警觉状态相关的方式在24小时内改变其脑电活动(ECoG)。在此,我们通过对与野生型小鼠(同窝出生)同时接受相同RHY处理的基因敲除(KO)小鼠进行ECoG记录,来探究这种生物碱在缺乏细胞粘附蛋白EPHA4的情况下是否会影响清醒/睡眠变量。我们发现,RHY减少了KO小鼠的清醒时间,增加了其慢波睡眠的时间,并改变了清醒和睡眠状态下ECoG活动的24小时时间进程。这些观察结果与RHY在野生型同窝动物中的报道效应相似,这有力地支持了RHY驱动的睡眠改变不依赖于EPHA4的存在。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a08/10572089/992964e5f3dc/zpad037_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a08/10572089/992964e5f3dc/zpad037_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a08/10572089/992964e5f3dc/zpad037_fig1.jpg

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本文引用的文献

1
Probing pathways by which rhynchophylline modifies sleep using spatial transcriptomics.利用空间转录组学探究钩藤碱调节睡眠的途径。
Biol Direct. 2023 May 5;18(1):21. doi: 10.1186/s13062-023-00377-7.
2
Rhynchophylline Administration Ameliorates Amyloid-β Pathology and Inflammation in an Alzheimer's Disease Transgenic Mouse Model.汉防己甲素给药可改善阿尔茨海默病转基因小鼠模型的淀粉样β病理和炎症。
ACS Chem Neurosci. 2021 Nov 17;12(22):4249-4256. doi: 10.1021/acschemneuro.1c00600. Epub 2021 Nov 5.
3
Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation.
钩藤碱的细胞效应及其与睡眠调节的关系。
Clocks Sleep. 2021 Jun 9;3(2):312-341. doi: 10.3390/clockssleep3020020.
4
Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype.中前额皮质中 EphA4-ephexin1 信号的增加在抑郁样表型中起作用。
Sci Rep. 2017 Aug 2;7(1):7133. doi: 10.1038/s41598-017-07325-2.
5
Shorter duration of non-rapid eye movement sleep slow waves in EphA4 knockout mice.EphA4基因敲除小鼠非快速眼动睡眠慢波的持续时间缩短。
J Sleep Res. 2017 Oct;26(5):539-546. doi: 10.1111/jsr.12532. Epub 2017 May 10.
6
Potent and Selective EphA4 Agonists for the Treatment of ALS.用于治疗肌萎缩侧索硬化症的强效且选择性的EphA4激动剂。
Cell Chem Biol. 2017 Mar 16;24(3):293-305. doi: 10.1016/j.chembiol.2017.01.006. Epub 2017 Feb 9.
7
EphA4 is Involved in Sleep Regulation but Not in the Electrophysiological Response to Sleep Deprivation.EphA4参与睡眠调节,但不参与对睡眠剥夺的电生理反应。
Sleep. 2016 Mar 1;39(3):613-24. doi: 10.5665/sleep.5538.
8
Are we using the right pharmacological tools to target EphA4?我们是否使用了正确的药理学工具来靶向 EphA4?
ACS Chem Neurosci. 2014 Dec 17;5(12):1146-7. doi: 10.1021/cn500285h. Epub 2014 Nov 18.
9
Blockade of EphA4 signaling ameliorates hippocampal synaptic dysfunctions in mouse models of Alzheimer's disease.阻断 EphA4 信号可改善阿尔茨海默病小鼠模型中海马突触功能障碍。
Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9959-64. doi: 10.1073/pnas.1405803111. Epub 2014 Jun 23.
10
Determination of protein-unbound rhynchiphylline brain distribution by microdialysis and ultra-performance liquid chromatography with tandem mass spectrometry.通过微透析和超高效液相色谱-串联质谱法测定游离型钩藤碱的脑内分布
Biomed Chromatogr. 2014 Jun;28(6):901-6. doi: 10.1002/bmc.3206.