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Sleep constitutes a third of human life and it is increasingly recognized as important for health. Over the past several decades, numerous genes have been identified to be involved in sleep regulation in animal models, but most of these genes when disturbed impair not only sleep but also health and physiological functions. Human natural short sleepers are individuals with lifelong short sleep and no obvious adverse outcomes associated with the lack of sleep. These traits appear to be heritable, and thus characterization of the genetic basis of natural short sleep provides an opportunity to study not only the genetic mechanism of human sleep but also the relationship between sleep and physiological function. This review focuses on the current understanding of mutations associated with the natural short sleep trait and the mechanisms by which they contribute to this trait.


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The molecular mechanism of natural short sleep: A path towards understanding why we need to sleep

Show Author's information Liubin Zheng1Luoying Zhang1,2( )
 Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China
 Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, Hubei, China

Abstract

Sleep constitutes a third of human life and it is increasingly recognized as important for health. Over the past several decades, numerous genes have been identified to be involved in sleep regulation in animal models, but most of these genes when disturbed impair not only sleep but also health and physiological functions. Human natural short sleepers are individuals with lifelong short sleep and no obvious adverse outcomes associated with the lack of sleep. These traits appear to be heritable, and thus characterization of the genetic basis of natural short sleep provides an opportunity to study not only the genetic mechanism of human sleep but also the relationship between sleep and physiological function. This review focuses on the current understanding of mutations associated with the natural short sleep trait and the mechanisms by which they contribute to this trait.

Keywords:

sleep duration, natural short sleep, short sleeper, gene, mutation
Received: 17 February 2022 Revised: 28 February 2022 Accepted: 04 March 2022 Published: 24 March 2022 Issue date: September 2022
References(42)
[1]
Grandner MA, Alfonso-Miller P, Fernandez-Mendoza J, et al. Sleep: Important considerations for the prevention of cardiovascular disease. Curr Opin Cardiol 2016, 31(5): 551–565.
[2]
Koren D, Taveras EM. Association of sleep disturbances with obesity, insulin resistance and the metabolic syndrome. Metabolism 2018, 84: 67–75.
[3]
Besedovsky L, Lange T, Born J. Sleep and immune function. Pflugers Arch 2012, 483(1): 121–137.
[4]
Goldstein AN, Walker MP. The role of sleep in emotional brain function. Annu Rev Clin Psychol 2014, 10: 679–708.
[5]
Spira AP, Chen-Edinboro LP, Wu MN, et al. Impact of sleep on the risk of cognitive decline and dementia. Curr Opin Psychiatry 2014, 27(6): 478–483.
[6]
Cappuccio FP, D'Elia L, Strazzullo P, et al. Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. Sleep 2010, 33(5): 585–592.
[7]
Cirelli C. The genetic and molecular regulation of sleep: from fruit flies to humans. Nat Rev Neurosci 2009, 10(8): 549–560.
[8]
Hendricks JC, Lu S, Kume K, et al. Gender dimorphism in the role of cycle (BMAL1) in rest, rest regulation, and longevity in Drosophila melanogaster. J Biol Rhythms 2003, 18(1): 12–25.
[9]
Koh K, Joiner WJ, Wu MN, et al. Identification of SLEEPLESS, a sleep-promoting factor. Science 2008, 321(5887): 372–376.
[10]
Nagy S, Maurer GW, Hentze JL, et al. AMPK signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance. PLoS Genet 2018, 14(12): e1007623.
[11]
Williams JA, Sathyanarayanan S, Hendricks JC, et al. Interaction between sleep and the immune response in Drosophila: a role for the NFkappaB relish. Sleep 2007, 30(4): 389–400.
[12]
Bushey D, Huber R, Tononi G, et al. Drosophila Hyperkinetic mutants have reduced sleep and impaired memory. J Neurosci 2007, 27(20): 5384–5393.
[13]
Ashbrook LH, Krystal AD, Fu YH, et al. Genetics of the human circadian clock and sleep homeostat. Neuropsychopharmacol 2020, 45(1): 45–54.
[14]
Fujimoto K, Shen M, Noshiro M, et al. Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins. Biochem Biophys Res Commun 2001, 280(1): 164–171.
[15]
Honma S, Kawamoto T, Takagi Y, et al. Dec1 and Dec2 are regulators of the mammalian molecular clock. Nature 2002, 419(6909): 841–844.
[16]
He Y, Jones CR, Fujiki N, et al. The transcriptional repressor DEC2 regulates sleep length in mammals. Science 2009, 325(5942): 866–870.
[17]
Pellegrino R, Kavakli IH, Goel N, et al. A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans. Sleep 2014, 37(8): 1327–1336.
[18]
Hirano A, Hsu PK, Zhang LY, et al. DEC2 modulates orexin expression and regulates sleep. Proc Natl Acad Sci USA 2018, 115(13): 3434–3439.
[19]
Shi GS, Xing LJ, Wu D, et al. A rare mutation of β1-adrenergic receptor affects sleep/wake behaviors. Neuron 2019, 103(6): 1044–1055.e7.
[20]
Brodde OE. Β-1 and β-2 adrenoceptor polymorphisms: functional importance, impact on cardiovascular diseases and drug responses. Pharmacol Ther 2008, 117(1): 1–29.
[21]
Berridge CW, Schmeichel BE, España RA. Noradrenergic modulation of wakefulness/arousal. Sleep Med Rev 2012, 16(2): 187–197.
[22]
Soriano-Ursúa MA, Trujillo-Ferrara JG, Correa-Basurto J, et al. Recent structural advances of β1 and β2 adrenoceptors yield keys for ligand recognition and drug design. J Med Chem 2013, 56(21): 8207–8223.
[23]
Xing LJ, Shi GS, Mostovoy Y, et al. Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation. Sci Transl Med 2019, 11(514): eaax2014.
[24]
Xu YL, Reinscheid RK, Huitron-Resendiz S, et al. Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Neuron 2004, 43(4): 487–497.
[25]
Zhao P, Shao YF, Zhang M, et al. Neuropeptide S promotes wakefulness through activation of the posterior hypothalamic histaminergic and orexinergic neurons. Neuroscience 2012, 207: 218–226.
[26]
Chauveau F, Claverie D, Lardant E, et al. Neuropeptide S promotes wakefulness through the inhibition of sleep-promoting ventrolateral preoptic nucleus neurons. Sleep 2020, 43(1): zsz189.
[27]
Clark SD, Duangdao DM, Schulz S, et al. Anatomical characterization of the neuropeptide S system in the mouse brain by in situ hybridization and immunohistochemistry. J Comp Neurol 2011, 519(10): 1867–1893.
[28]
Gent TC, Bandarabadi M, Herrera CG, et al. Thalamic dual control of sleep and wakefulness. Nat Neurosci 2018, 21(7): 974–984.
[29]
Reinscheid RK, Xu YL, Okamura N, et al. Pharmacological characterization of human and murine neuropeptide s receptor variants. J Pharmacol Exp Ther 2005, 315(3): 1338–1345.
[30]
Graves LA, Heller EA, Pack AI, et al. Sleep deprivation selectively impairs memory consolidation for contextual fear conditioning. Learn Mem 2003, 10(3): 168–176.
[31]
Shi GS, Yin C, Fan ZH, et al. Mutations in metabotropic glutamate receptor 1 contribute to natural short sleep trait. Curr Biol 2021, 31(1): 13–24.e4.
[32]
Niswender CM, Conn PJ. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 2010, 50: 295–322.
[33]
Ahnaou A, Langlois X, Steckler T, et al. Negative versus positive allosteric modulation of metabotropic glutamate receptors (mGluR5): indices for potential pro-cognitive drug properties based on EEG network oscillations and sleep-wake organization in rats. Psychopharmacol 2015, 232(6): 1107–1122.
[34]
Ahnaou A, Raeymaekers L, Steckler T, et al. Relevance of the metabotropic glutamate receptor (mGluR5) in the regulation of NREM-REM sleep cycle and homeostasis: evidence from mGluR5 (-/-) mice. Behav Brain Res 2015, 282: 218–226.
[35]
Page G, Khidir FAL, Pain S, et al. Group I metabotropic glutamate receptors activate the p70S6 kinase via both mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK 1/2) signaling pathways in rat striatal and hippocampal synaptoneurosomes. Neurochem Int 2006, 49(4): 413–421.
[37]
Mikhail C, Vaucher A, Jimenez S, et al. ERK signaling pathway regulates sleep duration through activity-induced gene expression during wakefulness. Sci Signal 2017, 10(463): eaai9219.
[37]
Hubbard J, Ruppert E, Gropp CM, et al. Non-circadian direct effects of light on sleep and alertness: lessons from transgenic mouse models. Sleep Med Rev 2013, 17(6): 445–452.
[38]
Yoon H, Baek HJ. External auditory stimulation as a non-pharmacological sleep aid. Sensors (Basel) 2022, 22(3): 1264.
[39]
Okamoto-Mizuno K, Mizuno K. Effects of thermal environment on sleep and circadian rhythm. J Physiol Anthropol 2012, 31: 14.
[40]
Liu LY, Deng H, Tang XP, et al. Specific electromagnetic radiation in the wireless signal range increases wakefulness in mice. Proc Natl Acad Sci USA 2021, 118(31): e2105838118.
[41]
Chaput JP. Sleep patterns, diet quality and energy balance. Physiol Behav 2014, 134: 86–91.
[42]
Pilcher JJ, Dorsey LL, Galloway SM, et al. Social isolation and sleep: manifestation during COVID-19 quarantines. Front Psychol 2021, 12: 810763.
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Publication history

Received: 17 February 2022
Revised: 28 February 2022
Accepted: 04 March 2022
Published: 24 March 2022
Issue date: September 2022

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© The authors 2022.

Acknowledgements

Acknowledgements

This work was supported by grants from the Ministry of Science and Technology of China (Grant No. 2021ZD0203202), and the Natural Science Foundation of China (Grant Nos. 31930021 and 32022035).

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