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慢性束缚应激中褪黑素相关功能障碍引发小鼠睡眠障碍。

Melatonin-related dysfunction in chronic restraint stress triggers sleep disorders in mice.

作者信息

Xia Tian-Ji, Wang Zhi, Jin Su-Wei, Liu Xin-Min, Liu Yong-Guang, Zhang Shan-Shan, Pan Rui-Le, Jiang Ning, Liao Yong-Hong, Yan Ming-Zhu, Du Li-Da, Chang Qi

机构信息

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Institute of Drug Discovery Technology, Ningbo University, Ningbo, China.

出版信息

Front Pharmacol. 2023 Jun 20;14:1210393. doi: 10.3389/fphar.2023.1210393. eCollection 2023.

Abstract

Stress may trigger sleep disorders and are also risk factors for depression. The study explored the melatonin-related mechanisms of stress-associated sleep disorders on a mouse model of chronic stress by exploring the alteration in sleep architecture, melatonin, and related small molecule levels, transcription and expression of melatonin-related genes as well as proteins. Mice undergoing chronic restraint stress modeling for 28 days showed body weight loss and reduced locomotor activity. Sleep fragmentation, circadian rhythm disorders, and insomnia exhibited in CRS-treated mice formed sleep disorders. Tryptophan and 5-hydroxytryptamine levels were increased in the hypothalamus, while melatonin level was decreased. The transcription and expression of melatonin receptors were reduced, and circadian rhythm related genes were altered. Expression of downstream effectors to melatonin receptors was also affected. These results identified sleep disorders in a mice model of chronic stress. The alteration of melatonin-related pathways was shown to trigger sleep disorders.

摘要

压力可能引发睡眠障碍,也是抑郁症的风险因素。该研究通过探究睡眠结构、褪黑素及相关小分子水平、褪黑素相关基因以及蛋白质的转录和表达变化,在慢性应激小鼠模型上探索了压力相关睡眠障碍的褪黑素相关机制。经历28天慢性束缚应激建模的小鼠出现体重减轻和运动活动减少。经慢性应激处理的小鼠出现睡眠片段化、昼夜节律紊乱和失眠,形成了睡眠障碍。下丘脑色氨酸和5-羟色胺水平升高,而褪黑素水平降低。褪黑素受体的转录和表达减少,昼夜节律相关基因发生改变。褪黑素受体下游效应器的表达也受到影响。这些结果确定了慢性应激小鼠模型中的睡眠障碍。结果表明,褪黑素相关通路的改变会引发睡眠障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5689/10318904/d0a087db5e87/fphar-14-1210393-g001.jpg

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