Sleep–wake characterization of double MT1/MT2 receptor knockout mice and comparison with MT1 and MT2 receptor knockout mice

Comai, Stefano; Ochoa‐Sanchez, Rafael; Gobbi, Gabriella

doi:10.1016/j.bbr.2013.01.008

Cited by 97 publications

(102 citation statements)

References 36 publications

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“…MT1 receptor knockout mice exhibited a significant increase in NREMS during the active/dark phase [18], whereas MT2 receptor knockout mice showed decreased NREMS duration [18]. Taken together, these knockout studies seem to suggest that MT1 and MT2 receptors modulate NREMS in an opposite manner [16]. By activating MT1 and MT2 receptors, melatonin and non-selective MT1/MT2 receptor agonists have shown to improve sleep quality, increase total sleep time, improve sleep efficiency and decrease sleep onset latency in insomnia patients.…”

Section: Effect Of Melatonin On Insomniamentioning

confidence: 82%

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A review of sleep disorders and melatonin

Xie

Chen

et al. 2017

Neurological Research

306

181

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Sleep disorders are a group of conditions that affect the ability to sleep well on a regular basis and cause significant impairments in social and occupational functions. Although currently approved medications are efficacious, they are far from satisfactory. Benzodiazepines, antidepressants, antihistamines and anxiolytics have the potential for dependence and addiction. Moreover, some of these medications can gradually impair cognition. Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous hormone produced by the pineal gland and released exclusively at night. Exogenous melatonin supplementation is well tolerated and has no obvious short-or long-term adverse effects. Melatonin has been shown to synchronize the circadian rhythms, and improve the onset, duration and quality of sleep. It is centrally involved in anti-oxidation, circadian rhythmicity maintenance, sleep regulation and neuronal survival. This narrative review aims to provide a comprehensive overview of various therapeutic functions of melatonin in insomnia, sleep-related breathing disorders, hypersomnolence, circadian rhythm sleep-wake disorders and parasomnias. Melatonin offers an alternative treatment to the currently available pharmaceutical therapies for sleep disorders with significantly less side effects.

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Section: Effect Of Melatonin On Insomniamentioning

confidence: 82%

“…By studying MT1 and MT2 receptor knockout mice, Comai et al showed that MT1 and MT2 receptors play different roles in sleep [16]. Merica et al demonstrated a connection between slow wave sleep and insomnia.…”

Section: Effect Of Melatonin On Insomniamentioning

confidence: 99%

A review of sleep disorders and melatonin

Xie

Chen

et al. 2017

Neurological Research

306

181

View full text Add to dashboard Cite

show abstract

“…In particular, during the light phase, REMS duration was decreased compared with wild-type mice (-46%) and NREMS duration was increased compared with MT 2 -/-mice (+33%). 101 This particular phenotype induced by the lack of the MT 1 receptor could explain the reason why a selective MT 2 receptor ligand is a more effective hypnotic agent than a nonselective MLT receptor ligand. We have indeed hypothesized that stimulation of the MT 2 receptor only increases NREMS, whereas MT 1 receptor activation increases REMS, while slightly decreasing NREMS.…”

Section: Mt 2 Knockout Mice and Sleepmentioning

confidence: 99%

Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology

Comai

Gobbi

2014

J Psychiatry Neurosci

Self Cite

153

126

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IntroductionMelatonin (MLT) is a neurohormone synthesized from serotonin (5-HT) and secreted foremost by the mammalian pineal gland following a distinct circadian rhythm with the acrophase during the dark phase and the nadir during the light phase in both diurnal and nocturnal species.1 A typical human adult's average daytime and nighttime levels of blood MLT are approximately 10 pg/mL and 60 pg/mL, respectively.2 Its production is controlled through the suprachiasmatic nucleus (SCN) by the photoperiod, peaking at night and dropping during the day. Melatonin is involved in numerous physiologic processes, including circadian rhythms, mood regulation, anxiety, sleep, appetite, immune responses and cardiac functions. 3,4 Most of the effects of MLT in the brain result from the activation of 2 high-affinity G-protein coupled receptors (GPCRs), MT 1 and MT 2 .5 Of note, GPCRs have a proven history of being excellent therapeutic targets. Recent market analyses indicate that 40%-50% of modern drugs and almost 25% of the top 200 best-selling drugs target GPCRs. 6 In addition to these high-affinity MLT receptors, another low-affinity MLT binding site, MT 3 , has recently been characterized as an MLT-sensitive form of the human enzyme quinone reductase 2. 7 The functional characterization of MT 1 and MT 2 receptors in target tissues is hampered by the paucity of selective MT 1 and MT 2 receptor ligands. Structural Background: Melatonin (MLT) is a pleiotropic neurohormone controlling many physiological processes and whose dysfunction may contribute to several different diseases, such as neurodegenerative diseases, circadian and mood disorders, insomnia, type 2 diabetes and pain. Melatonin is synthesized by the pineal gland during the night and acts through 2 G-protein coupled receptors (GPCRs), MT 1 (MEL1a) and MT 2 (MEL1b). Although a bulk of research has examined the physiopathological effects of MLT, few studies have investigated the selective role played by MT 1 and MT 2 receptors. Here we have reviewed current knowledge about the implications of MT 2 receptors in brain functions. Methods: We searched PubMed, Web of Science, Scopus, Google Scholar and articles reference lists for studies on MT 2 receptor ligands in sleep, anxiety, neuropsychiatric diseases and psychopharmacology, including genetic studies on the MTNR1B gene, which encodes the melatonin MT 2 receptor. Results: These studies demonstrate that MT 2 receptors are involved in the pathophysiology and pharmacology of sleep disorders, anxiety, depression, Alzheimer disease and pain and that selective MT 2 receptor agonists show hypnotic and anxiolytic properties. Limitations: Studies examining the role of MT 2 receptors in psychopharmacology are still limited. Conclusion: The development of novel selective MT 2 receptor ligands, together with further preclinical in vivo studies, may clarify the role of this receptor in brain function and psychopharmacology. The superfamily of GPCRs has proven to be among the most successful drug targets and, consequently, M...

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“…Связываясь с цитозольным кальмодулином, гормон может непосредственно влиять на кальцие-вые сигналы путём взаимодействия с ферментами, такими как аденилатциклаза и фосфодиэстераза, а также со структурными белками [1]. Эксперименталь-ными исследованиями показано, что нокаутирование МТ1-рецептора у мышей увеличивает длительность медленного сна (NREM), в то время как нокаутиро-вание МТ2-рецептора его сокращает, таким образом в процессе сна рецепторами выполняются противо-положные роли [15,31].…”

Section: Abstract: Circadian Rhythms Melatonin Menopause Sleep DIunclassified

Chronobiological Aspects of Sleep Disorders in Menopausal Women: The Role of Melatonin (Literature Review)

Семёнова¹,

Semyonova²

2017

Acta Biomedica Scientifica

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Sleep–wake characterization of double MT1/MT2 receptor knockout mice and comparison with MT1 and MT2 receptor knockout mice

Cited by 97 publications

References 36 publications

A review of sleep disorders and melatonin

A review of sleep disorders and melatonin

Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology

Chronobiological Aspects of Sleep Disorders in Menopausal Women: The Role of Melatonin (Literature Review)

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