![]() The central actions of melatonin on circadian rhythms focus on the hypothalamus, especially the suprachiasmatic nucleus (SCN) ( Slominski et al., 2012). Melatonin regulates the circadian rhythm and affects sleep architecture. Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous hormone that interacts with membrane melatonin receptors MT1 and MT2, two different types of G-protein-coupled receptors expressed both in brain regions and peripheral tissues ( Pandi-Perumal et al., 2008 Pohanka, 2022). Sleep is regulated by circadian and homeostatic processes ( Saper et al., 2005 Borbély, 2022). Sleep disorders are the most prominent symptom in depressive patients ( Fang et al., 2019). ![]() In addition, many neuropsychiatric disorders, especially depression, can lead to sleep disorders. ![]() Stressful life events, related to work/school living, family, health, or indeterminate with negative emotional valence, are the most frequent triggers of insomnia ( Bastien et al., 2004 Drake et al., 2014). Increased levels of stress at night lead to decreases in slow wave sleep, sleep efficiency, and general sleep quality ( Kim and Dimsdale, 2007). A study has indicated that poorer sleep is associated with elevated feelings of stress in both individuals with sleep disorders and individuals from the general population ( Demichelis et al., 2022). Predisposing factors for sleep disorders include age, sex, environment, stress, irregular sleep-wake schedule, etc ( Billings et al., 2020 Meyer et al., 2022). Sleep is sensitive and can easily be affected. Sleep disorders are tightly linked with functional consequences like decreased attention and concentration, an increased risk of disease, lower work productivity, etc ( Battle, 2013). Circadian rhythm disorders include advanced or delayed sleep phase disorder and irregular sleep-wake rhythm ( Allega et al., 2018). Insomnia, the most prevalent type of sleep disorder, is characterized by difficulty in sleep initiation and maintenance ( Riemann et al., 2020). Sleep disorders include insomnia, narcolepsy, sleep apnea syndrome, circadian rhythm disorders, etc., affecting up to 40.49% population during 2019–2021 and becoming a significant public health concern ( Jahrami et al., 2022). Sleep disorders are commonly associated with neurological pathogenesis and may indicate some neurodegenerative processes ( Musiek and Holtzman, 2016). Sleep affects various physiological homeostasis and has a pivotal role in regulating the central nervous system functions ( Tononi and Cirelli, 2014 Cuddapah et al., 2019). The alteration of melatonin-related pathways was shown to trigger sleep disorders. These results identified sleep disorders in a mice model of chronic stress. Expression of downstream effectors to melatonin receptors was also affected. The transcription and expression of melatonin receptors were reduced, and circadian rhythm related genes were altered. Tryptophan and 5-hydroxytryptamine levels were increased in the hypothalamus, while melatonin level was decreased. Sleep fragmentation, circadian rhythm disorders, and insomnia exhibited in CRS-treated mice formed sleep disorders. ![]() Mice undergoing chronic restraint stress modeling for 28 days showed body weight loss and reduced locomotor activity. 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. Stress may trigger sleep disorders and are also risk factors for depression. 4Department of Surgery, University of Toronto, Toronto, TO, Canada.3Institute of Molecular Medicine and Innovative Pharmaceutics, Qingdao University, Qingdao, China.2Institute of Drug Discovery Technology, Ningbo University, Ningbo, China.1Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.Tian-Ji Xia 1, Zhi Wang 1, Su-Wei Jin 1, Xin-Min Liu 2, Yong-Guang Liu 1, Shan-Shan Zhang 1, Rui-Le Pan 1, Ning Jiang 1, Yong-Hong Liao 1, Ming-Zhu Yan 1*, Li-Da Du 3,4* and Qi Chang 1* ![]()
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