Skip to main content
SpringerLink
Log in

Clock genes and sleep

  • Invited Review
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

In most species—from cyanobacteria to humans—endogenous clocks have evolved that drive 24-h rhythms of behavior and physiology. In mammals, these circadian rhythms are regulated by a hierarchical network of cellular oscillators controlled by a set of clock genes organized in a system of interlocked transcriptional feedback loops. One of the most prominent outputs of the circadian system is the synchronization of the sleep–wake cycle with external (day-) time. Clock genes also have a strong impact on many other biological functions, such as memory formation, energy metabolism, and immunity. Remarkably, large overlaps exist between clock gene and sleep (loss) mediated effects on these processes. This review summarizes sleep clock gene interactions for these three phenomena, highlighting potential mediators linking sleep and/or clock function to physiological output in an attempt to better understand the complexity of diurnal adaptation and its consequences for health and disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Allebrandt KV et al (2010) CLOCK gene variants associate with sleep duration in two independent populations. Biol Psychiatry 67(11):1040–1047

    Article  PubMed  CAS  Google Scholar 

  2. Antoch MP et al (1997) Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Cell 89(4):655–667

    Article  PubMed  CAS  Google Scholar 

  3. Arble DM et al (2009) Circadian timing of food intake contributes to weight gain. Obesity (Silver Spring) 17(11):2100–2102

    Article  Google Scholar 

  4. Archer SN et al (2003) A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference. Sleep 26(4):413–415

    PubMed  Google Scholar 

  5. Archer SN et al (2008) Inter-individual differences in habitual sleep timing and entrained phase of endogenous circadian rhythms of BMAL1, PER2 and PER3 mRNA in human leukocytes. Sleep 31(5):608–617

    PubMed  Google Scholar 

  6. Archer SN et al (2010) Polymorphism in the PER3 promoter associates with diurnal preference and delayed sleep phase disorder. Sleep 33(5):695–701

    Google Scholar 

  7. Arjona A, Sarkar DK (2006) The circadian gene mPer2 regulates the daily rhythm of IFN-gamma. J Interferon Cytokine Res 26(9):645–649

    Article  PubMed  CAS  Google Scholar 

  8. Arjona A, Sarkar DK (2006) Evidence supporting a circadian control of natural killer cell function. Brain Behav Immun 20(5):469–476

    Article  PubMed  CAS  Google Scholar 

  9. Balestrieri S, D’Onofrio G, Giuditta A (1980) Deprivation of paradoxical sleep. Effect on weight and nucleic acid content of liver and brain. Neurochem Res 5(12):1251–1264

    Article  PubMed  CAS  Google Scholar 

  10. Barnes CA et al (1977) Circadian rhythm of synaptic excitability in rat and monkey central nervous system. Science 197(4298):91–92

    Article  PubMed  CAS  Google Scholar 

  11. Bodosi B et al (2004) Rhythms of ghrelin, leptin, and sleep in rats: effects of the normal diurnal cycle, restricted feeding, and sleep deprivation. Am J Physiol Regul Integr Comp Physiol 287(5):R1071–R1079

    Article  PubMed  CAS  Google Scholar 

  12. Bollinger T et al (2009) Sleep-dependent activity of T cells and regulatory T cells. Clin Exp Immunol 155(2):231–238

    Article  PubMed  CAS  Google Scholar 

  13. Borbely AA (1982) A two process model of sleep regulation. Hum Neurobiol 1(3):195–204

    PubMed  CAS  Google Scholar 

  14. Born J et al (1997) Effects of sleep and circadian rhythm on human circulating immune cells. J Immunol 158(9):4454–4464

    PubMed  CAS  Google Scholar 

  15. Bramham CR, Srebro B (1989) Synaptic plasticity in the hippocampus is modulated by behavioral state. Brain Res 493(1):74–86

    Article  PubMed  CAS  Google Scholar 

  16. Bryant PA, Trinder J, Curtis N (2004) Sick and tired: does sleep have a vital role in the immune system? Nat Rev Immunol 4(6):457–467

    Article  PubMed  CAS  Google Scholar 

  17. Bunger MK et al (2000) Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103(7):1009–1017

    Article  PubMed  CAS  Google Scholar 

  18. Carpen JD et al (2005) A single-nucleotide polymorphism in the 5′-untranslated region of the hPER2 gene is associated with diurnal preference. J Sleep Res 14(3):293–297

    Article  PubMed  Google Scholar 

  19. Carpen JD et al (2006) A silent polymorphism in the PER1 gene associates with extreme diurnal preference in humans. J Hum Genet 51(12):1122–1125

    Article  PubMed  CAS  Google Scholar 

  20. Castanon-Cervantes O et al (2010) Dysregulation of inflammatory responses by chronic circadian disruption. J Immunol 185(10):5796–5805

    Article  PubMed  CAS  Google Scholar 

  21. Cavadini G et al (2007) TNF-alpha suppresses the expression of clock genes by interfering with E-box-mediated transcription. Proc Natl Acad Sci USA 104(31):12843–12848

    Article  PubMed  CAS  Google Scholar 

  22. Chaudhury D, Wang LM, Colwell CS (2005) Circadian regulation of hippocampal long-term potentiation. J Biol Rhythms 20(3):225–236

    Article  PubMed  Google Scholar 

  23. Chaudhury D et al (2008) Select cognitive deficits in vasoactive intestinal peptide deficient mice. BMC Neurosci 9:63

    Article  PubMed  CAS  Google Scholar 

  24. Cheng MY et al (2002) Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature 417(6887):405–410

    Article  PubMed  CAS  Google Scholar 

  25. Chung BY et al (2009) The GABA(A) receptor RDL acts in peptidergic PDF neurons to promote sleep in Drosophila. Curr Biol 19(5):386–390

    Article  PubMed  CAS  Google Scholar 

  26. Cyran SA et al (2003) vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock. Cell 112(3):329–341

    Article  PubMed  CAS  Google Scholar 

  27. Daan S, Beersma DG, Borbely AA (1984) Timing of human sleep: recovery process gated by a circadian pacemaker. Am J Physiol 246(2 Pt 2):R161–R183

    PubMed  CAS  Google Scholar 

  28. Danguir J, Nicolaidis S (1979) Dependence of sleep on nutrients’ availability. Physiol Behav 22(4):735–740

    Article  PubMed  CAS  Google Scholar 

  29. Date Y et al (2000) Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 141(11):4255–4261

    Article  PubMed  CAS  Google Scholar 

  30. Deboer T et al (2003) Sleep states alter activity of suprachiasmatic nucleus neurons. Nat Neurosci 6(10):1086–1090

    Article  PubMed  CAS  Google Scholar 

  31. Deboer T, Detari L, Meijer JH (2007) Long term effects of sleep deprivation on the mammalian circadian pacemaker. Sleep 30(3):257–262

    PubMed  Google Scholar 

  32. Diekelmann S et al (2008) Sleep loss produces false memories. PLoS One 3(10):e3512

    Article  PubMed  CAS  Google Scholar 

  33. Diekelmann S, Born J, Wagner U (2010) Sleep enhances false memories depending on general memory performance. Behav Brain Res 208(2):425–429

    Article  PubMed  Google Scholar 

  34. Dijk DJ, Czeisler CA (1995) Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans. J Neurosci Off J Soc Neurosci 15(5 Pt 1):3526–3538

    CAS  Google Scholar 

  35. Dimitrov S et al (2007) Number and function of circulating human antigen presenting cells regulated by sleep. Sleep 30(4):401–411

    PubMed  Google Scholar 

  36. Dimitrov S et al (2009) Cortisol and epinephrine control opposing circadian rhythms in T cell subsets. Blood 113(21):5134–5143

    Article  PubMed  CAS  Google Scholar 

  37. Dimitrov S, Lange T, Born J (2010) Selective mobilization of cytotoxic leukocytes by epinephrine. J Immunol 184(1):503–511

    Article  PubMed  CAS  Google Scholar 

  38. Drake CL et al (2000) Effects of an experimentally induced rhinovirus cold on sleep, performance, and daytime alertness. Physiol Behav 71(1–2):75–81

    Article  PubMed  CAS  Google Scholar 

  39. Dudley CA et al (2003) Altered patterns of sleep and behavioral adaptability in NPAS2-deficient mice. Science 301(5631):379–383

    Article  PubMed  CAS  Google Scholar 

  40. Dzaja A et al (2004) Sleep enhances nocturnal plasma ghrelin levels in healthy subjects. Am J Physiol Endocrinol Metab 286(6):E963–E967

    Article  PubMed  CAS  Google Scholar 

  41. Eckel-Mahan KL et al (2008) Circadian oscillation of hippocampal MAPK activity and cAmp: implications for memory persistence. Nat Neurosci 11(9):1074–1082

    Article  PubMed  CAS  Google Scholar 

  42. Everson CA (1993) Sustained sleep deprivation impairs host defense. Am J Physiol 265(5 Pt 2):R1148–R1154

    PubMed  CAS  Google Scholar 

  43. Everson CA, Toth LA (2000) Systemic bacterial invasion induced by sleep deprivation. Am J Physiol Regul Integr Comp Physiol 278(4):R905–R916

    PubMed  CAS  Google Scholar 

  44. Everson CA, Crowley WR (2004) Reductions in circulating anabolic hormones induced by sustained sleep deprivation in rats. Am J Physiol Endocrinol Metab 286(6):E1060–E1070

    Article  PubMed  CAS  Google Scholar 

  45. Franken P et al (2000) The transcription factor DBP affects circadian sleep consolidation and rhythmic EEG activity. J Neurosci 20(2):617–625

    PubMed  CAS  Google Scholar 

  46. Franken P et al (2006) NPAS2 as a transcriptional regulator of non-rapid eye movement sleep: genotype and sex interactions. Proc Natl Acad Sci USA 103(18):7118–7123

    Article  PubMed  CAS  Google Scholar 

  47. Franken P, Dijk DJ (2009) Circadian clock genes and sleep homeostasis. Eur J Neurosci 29(9):1820–1829

    Article  PubMed  CAS  Google Scholar 

  48. Gallego M, Virshup DM (2007) Post-translational modifications regulate the ticking of the circadian clock. Nat Rev Mol Cell Biol 8(2):139–148

    Article  PubMed  CAS  Google Scholar 

  49. Gangwisch JE et al (2005) Inadequate sleep as a risk factor for obesity: analyses of the NHANES I. Sleep 28(10):1289–1296

    PubMed  Google Scholar 

  50. Garcia JA et al (2000) Impaired cued and contextual memory in NPAS2-deficient mice. Science 288(5474):2226–2230

    Article  PubMed  CAS  Google Scholar 

  51. Gerstner JR (2010) The aging clock: to 'BMAL'icious toward learning and memory. Aging 2(5):251–254

    PubMed  CAS  Google Scholar 

  52. Gottlieb DJ et al (2005) Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med 165(8):863–867

    Article  PubMed  Google Scholar 

  53. Green CB et al (2007) Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity. Proc Natl Acad Sci USA 104(23):9888–9893

    Article  PubMed  CAS  Google Scholar 

  54. Grimble RF (2002) Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care 5(5):551–559

    Article  PubMed  CAS  Google Scholar 

  55. Guess J et al (2009) Circadian disruption, Per3, and human cytokine secretion. Integr Cancer Ther 8(4):329–336

    Article  PubMed  CAS  Google Scholar 

  56. Hardin PE (2005) The circadian timekeeping system of Drosophila. Curr Biol 15(17):R714–R722

    Article  PubMed  CAS  Google Scholar 

  57. Hardin PE, Hall JC, Rosbash M (1990) Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343(6258):536–540

    Article  PubMed  CAS  Google Scholar 

  58. Harmar AJ et al (2002) The VPAC(2) receptor is essential for circadian function in the mouse suprachiasmatic nuclei. Cell 109(4):497–508

    Article  PubMed  CAS  Google Scholar 

  59. He Y et al (2009) The transcriptional repressor DEC2 regulates sleep length in mammals. Science 325(5942):866–870

    Article  PubMed  CAS  Google Scholar 

  60. Hendricks JC et al (2000) Rest in Drosophila is a sleep-like state. Neuron 25(1):129–138

    Article  PubMed  CAS  Google Scholar 

  61. Hendricks JC et al (2003) Gender dimorphism in the role of cycle (BMAL1) in rest, rest regulation, and longevity in Drosophila melanogaster. J Biol Rhythms 18(1):12–25

    Article  PubMed  CAS  Google Scholar 

  62. Honma S et al (2002) Dec1 and Dec2 are regulators of the mammalian molecular clock. Nature 419(6909):841–844

    Article  PubMed  CAS  Google Scholar 

  63. Horne JA, McGrath MJ (1984) The consolidation hypothesis for REM sleep function: stress and other confounding factors—a review. Biol Psychol 18(3):165–184

    Article  PubMed  CAS  Google Scholar 

  64. Hotamisligil GS, Erbay E (2008) Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 8(12):923–934

    Article  PubMed  CAS  Google Scholar 

  65. Hu WP et al (2007) Altered circadian and homeostatic sleep regulation in prokineticin 2-deficient mice. Sleep 30(3):247–256

    PubMed  Google Scholar 

  66. Hucking K et al (2003) Burst-like control of lipolysis by the sympathetic nervous system in vivo. J Clin Invest 111(2):257–264

    PubMed  CAS  Google Scholar 

  67. Ibuka N, Nihonmatsu I, Sekiguchi S (1980) Sleep–wakefulness rhythms in mice after suprachiasmatic nucleus lesions. Waking Sleeping 4(2):167–173

    PubMed  CAS  Google Scholar 

  68. Jenkins JG, Dallenbach KM (1924) Obliviscence during sleep and waking. Am J Psychol 35:605–612

    Article  Google Scholar 

  69. Jennings JR et al (2007) Self-reported sleep quality is associated with the metabolic syndrome. Sleep 30(2):219–223

    PubMed  Google Scholar 

  70. Jilg A et al (2010) Temporal dynamics of mouse hippocampal clock gene expression support memory processing. Hippocampus 20(3):377–388

    PubMed  CAS  Google Scholar 

  71. King DP et al (1997) Positional cloning of the mouse circadian clock gene. Cell 89(4):641–653

    Article  PubMed  CAS  Google Scholar 

  72. Ko HW, Jiang J, Edery I (2002) Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime. Nature 420(6916):673–678

    Article  PubMed  CAS  Google Scholar 

  73. Kojima M et al (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402(6762):656–660

    Article  PubMed  CAS  Google Scholar 

  74. Kondratov RV et al (2006) Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock. Genes Dev 20(14):1868–1873

    Article  PubMed  CAS  Google Scholar 

  75. Konopka RJ, Benzer S (1971) Clock mutants of Drosophila melanogaster. Proc Natl Acad Sci USA 68(9):2112–2116

    Article  PubMed  CAS  Google Scholar 

  76. Kopp C et al (2002) Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant mice. Eur J Neurosci 16(6):1099–1106

    Article  PubMed  Google Scholar 

  77. Korman M et al (2007) Daytime sleep condenses the time course of motor memory consolidation. Nat Neurosci 10(9):1206–1213

    Article  PubMed  CAS  Google Scholar 

  78. Lahl O et al (2008) An ultra short episode of sleep is sufficient to promote declarative memory performance. J Sleep Res 17(1):3–10

    Article  PubMed  Google Scholar 

  79. Lamia KA, Storch KF, Weitz CJ (2008) Physiological significance of a peripheral tissue circadian clock. Proc Natl Acad Sci USA 105(39):15172–15177

    Article  PubMed  CAS  Google Scholar 

  80. Lange T, Dimitrov S, Born J (2010) Effects of sleep and circadian rhythm on the human immune system. Ann N Y Acad Sci 1193:48–59

    Article  PubMed  CAS  Google Scholar 

  81. Laposky A et al (2005) Deletion of the mammalian circadian clock gene BMAL1/Mop3 alters baseline sleep architecture and the response to sleep deprivation. Sleep 28(4):395–409

    PubMed  Google Scholar 

  82. Lau P et al (2004) RORalpha regulates the expression of genes involved in lipid homeostasis in skeletal muscle cells: caveolin-3 and CPT-1 are direct targets of ROR. J Biol Chem 279(35):36828–36840

    Article  PubMed  CAS  Google Scholar 

  83. Lee C et al (2001) Posttranslational mechanisms regulate the mammalian circadian clock. Cell 107(7):855–867

    Article  PubMed  CAS  Google Scholar 

  84. Lee ML, Swanson BE, de la Iglesia HO (2009) Circadian timing of REM sleep is coupled to an oscillator within the dorsomedial suprachiasmatic nucleus. Curr Biol 19(10):848–852

    Article  PubMed  CAS  Google Scholar 

  85. Leproult R et al (1997) Sleep loss results in an elevation of cortisol levels the next evening. Sleep 20(10):865–870

    PubMed  CAS  Google Scholar 

  86. Li JD et al (2006) Attenuated circadian rhythms in mice lacking the prokineticin 2 gene. J Neurosci 26(45):11615–11623

    Article  PubMed  CAS  Google Scholar 

  87. Lim C et al (2007) Clockwork orange encodes a transcriptional repressor important for circadian-clock amplitude in Drosophila. Curr Biol 17(12):1082–1089

    Article  PubMed  CAS  Google Scholar 

  88. Liu J et al (2006) The circadian clock Period 2 gene regulates gamma interferon production of NK cells in host response to lipopolysaccharide-induced endotoxic shock. Infect Immun 74(8):4750–4756

    Article  PubMed  CAS  Google Scholar 

  89. Lonnqvist F et al (1995) Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med 1(9):950–953

    Article  PubMed  CAS  Google Scholar 

  90. Lopez-Molina L et al (1997) The DBP gene is expressed according to a circadian rhythm in the suprachiasmatic nucleus and influences circadian behavior. EMBO J 16(22):6762–6771

    Article  PubMed  CAS  Google Scholar 

  91. Luo Y et al (2009) Expression profiling reveals a positive regulation by mPer2 on circadian rhythm of cytotoxicity receptors: Ly49C and Nkg2d. Chronobiol Int 26(8):1514–1544

    Article  PubMed  CAS  Google Scholar 

  92. Maestroni GJ, Conti A, Pierpaoli W (1986) Role of the pineal gland in immunity. Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone. J Neuroimmunol 13(1):19–30

    Article  PubMed  CAS  Google Scholar 

  93. Majde JA, Krueger JM (2005) Links between the innate immune system and sleep. J Allergy Clin Immunol 116(6):1188–1198

    Article  PubMed  CAS  Google Scholar 

  94. Marangou AG et al (1988) Hormonal effects of norepinephrine on acute glucose disposal in humans: a minimal model analysis. Metabolism 37(9):885–891

    Article  PubMed  CAS  Google Scholar 

  95. Marshall L, Born J (2007) The contribution of sleep to hippocampus-dependent memory consolidation. Trends Cogn Sci 11(10):442–450

    Article  PubMed  Google Scholar 

  96. Martin SJ, Grimwood PD, Morris RG (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23:649–711

    Article  PubMed  CAS  Google Scholar 

  97. Matsumoto Y et al (2001) Total sleep deprivation induces an acute and transient increase in NK cell activity in healthy young volunteers. Sleep 24(7):804–809

    PubMed  CAS  Google Scholar 

  98. Maury E, Ramsey KM, Bass J (2010) Circadian rhythms and metabolic syndrome: from experimental genetics to human disease. Circ Res 106(3):447–462

    Article  PubMed  CAS  Google Scholar 

  99. Mednick S, Nakayama K, Stickgold R (2003) Sleep-dependent learning: a nap is as good as a night. Nat Neurosci 6(7):697–698

    Article  PubMed  CAS  Google Scholar 

  100. Mistlberger RE et al (1983) Recovery sleep following sleep deprivation in intact and suprachiasmatic nuclei-lesioned rats. Sleep 6(3):217–233

    PubMed  CAS  Google Scholar 

  101. Mitsui S et al (2001) Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory mechanism. Genes Dev 15(8):995–1006

    Article  PubMed  CAS  Google Scholar 

  102. Mulder H et al (2009) Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene. Diabetologia 52(7):1240–1249

    Article  PubMed  CAS  Google Scholar 

  103. Murakami N et al (2002) Role for central ghrelin in food intake and secretion profile of stomach ghrelin in rats. J Endocrinol 174(2):283–288

    Article  PubMed  CAS  Google Scholar 

  104. Nambu T et al (1999) Distribution of orexin neurons in the adult rat brain. Brain Res 827(1–2):243–260

    Article  PubMed  CAS  Google Scholar 

  105. Naylor E et al (2000) The circadian clock mutation alters sleep homeostasis in the mouse. J Neurosci 20(21):8138–8143

    PubMed  CAS  Google Scholar 

  106. Nilsson PM et al (2004) Incidence of diabetes in middle-aged men is related to sleep disturbances. Diabetes Care 27(10):2464–2469

    Article  PubMed  Google Scholar 

  107. Nishikawa Y, Shibata S, Watanabe S (1995) Circadian changes in long-term potentiation of rat suprachiasmatic field potentials elicited by optic nerve stimulation in vitro. Brain Res 695(2):158–162

    Article  PubMed  CAS  Google Scholar 

  108. Oishi K, Shirai H, Ishida N (2005) CLOCK is involved in the circadian transactivation of peroxisome-proliferator-activated receptor alpha (PPARalpha) in mice. Biochem J 386(Pt 3):575–581

    PubMed  CAS  Google Scholar 

  109. Okano S et al (2009) Unusual circadian locomotor activity and pathophysiology in mutant CRY1 transgenic mice. Neurosci Lett 451(3):246–251

    Article  PubMed  CAS  Google Scholar 

  110. Oster H et al (2006) The circadian rhythm of glucocorticoids is regulated by a gating mechanism residing in the adrenal cortical clock. Cell Metab 4(2):163–173

    Article  PubMed  CAS  Google Scholar 

  111. Pallier PN et al (2007) Pharmacological imposition of sleep slows cognitive decline and reverses dysregulation of circadian gene expression in a transgenic mouse model of Huntington’s disease. J Neurosci Off J Soc Neurosci 27(29):7869–7878

    Article  CAS  Google Scholar 

  112. Patel SR et al (2004) A prospective study of sleep duration and mortality risk in women. Sleep 27(3):440–444

    PubMed  Google Scholar 

  113. Peschke E et al (2006) Diabetic Goto Kakizaki rats as well as type 2 diabetic patients show a decreased diurnal serum melatonin level and an increased pancreatic melatonin-receptor status. J Pineal Res 40(2):135–143

    Article  PubMed  CAS  Google Scholar 

  114. Petrzilka S et al (2009) Clock gene modulation by TNF-alpha depends on calcium and p38 MAP kinase signaling. J Biol Rhythms 24(4):283–294

    Article  PubMed  CAS  Google Scholar 

  115. Prather AA et al (2009) Normative variation in self-reported sleep quality and sleep debt is associated with stimulated pro-inflammatory cytokine production. Biol Psychol 82(1):12–17

    Article  PubMed  Google Scholar 

  116. Preitner N et al (2002) The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110(2):251–260

    Article  PubMed  CAS  Google Scholar 

  117. Price JL et al (1998) Double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation. Cell 94(1):83–95

    Article  PubMed  CAS  Google Scholar 

  118. Rasch B et al (2009) Pharmacological REM sleep suppression paradoxically improves rather than impairs skill memory. Nat Neurosci 12(4):396–397

    Article  PubMed  CAS  Google Scholar 

  119. Rechtschaffen A, Bergmann BM (1995) Sleep deprivation in the rat by the disk-over-water method. Behav Brain Res 69(1–2):55–63

    Article  PubMed  CAS  Google Scholar 

  120. Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418(6901):935–941

    Article  PubMed  CAS  Google Scholar 

  121. Riemersma-van der Lek RF et al (2008) Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA 299(22):2642–2655

    Article  PubMed  CAS  Google Scholar 

  122. Roberge C et al (2007) Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity. Am J Physiol Endocrinol Metab 293(6):E1465–E1478

    Article  PubMed  CAS  Google Scholar 

  123. Romcy-Pereira R, Pavlides C (2004) Distinct modulatory effects of sleep on the maintenance of hippocampal and medial prefrontal cortex LTP. Eur J Neurosci 20(12):3453–3462

    Article  PubMed  Google Scholar 

  124. Rossner MJ et al (2008) Disturbed clockwork resetting in Sharp-1 and Sharp-2 single and double mutant mice. PLoS One 3(7):e2762

    Article  PubMed  CAS  Google Scholar 

  125. Rudic RD et al (2004) BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol 2(11):e377

    Article  PubMed  CAS  Google Scholar 

  126. Sakurai T (2005) Roles of orexin/hypocretin in regulation of sleep/wakefulness and energy homeostasis. Sleep Med Rev 9(4):231–241

    Article  PubMed  Google Scholar 

  127. Sato TK et al (2004) A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron 43(4):527–537

    Article  PubMed  CAS  Google Scholar 

  128. Schoeller DA et al (1997) Entrainment of the diurnal rhythm of plasma leptin to meal timing. J Clin Invest 100(7):1882–1887

    Article  PubMed  CAS  Google Scholar 

  129. Schwegler H, Crusio WE, Brust I (1990) Hippocampal mossy fibers and radial-maze learning in the mouse: a correlation with spatial working memory but not with non-spatial reference memory. Neuroscience 34(2):293–298

    Article  PubMed  CAS  Google Scholar 

  130. Scott EM, Carter AM, Grant PJ (2008) Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man. Int J Obes (Lond) 32(4):658–662

    Article  CAS  Google Scholar 

  131. Shaw PJ et al (2000) Correlates of sleep and waking in Drosophila melanogaster. Science 287(5459):1834–1837

    Article  PubMed  CAS  Google Scholar 

  132. Shaw PJ et al (2002) Stress response genes protect against lethal effects of sleep deprivation in Drosophila. Nature 417(6886):287–291

    Article  PubMed  CAS  Google Scholar 

  133. Sheward WJ et al (2010) Circadian control of mouse heart rate and blood pressure by the suprachiasmatic nuclei: behavioral effects are more significant than direct outputs. PLoS One 5(3):e9783

    Article  PubMed  CAS  Google Scholar 

  134. Shimba S et al (2005) Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis. Proc Natl Acad Sci USA 102(34):12071–12076

    Article  PubMed  CAS  Google Scholar 

  135. Shiromani PJ et al (2004) Sleep rhythmicity and homeostasis in mice with targeted disruption of mPeriod genes. Am J Physiol Regul Integr Comp Physiol 287(1):R47–R57

    Article  PubMed  CAS  Google Scholar 

  136. Simon C et al (1998) Circadian and ultradian variations of leptin in normal man under continuous enteral nutrition: relationship to sleep and body temperature. J Clin Endocrinol Metab 83(6):1893–1899

    Article  PubMed  CAS  Google Scholar 

  137. Slieker LJ et al (1996) Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP. J Biol Chem 271(10):5301–5304

    Article  PubMed  CAS  Google Scholar 

  138. Smith C (2001) Sleep states and memory processes in humans: procedural versus declarative memory systems. Sleep Med Rev 5(6):491–506

    Article  PubMed  Google Scholar 

  139. Spiegel K, Leproult R, Van Cauter E (1999) Impact of sleep debt on metabolic and endocrine function. Lancet 354(9188):1435–1439

    Article  PubMed  CAS  Google Scholar 

  140. Spiegel K et al (2004) Brief communication: sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med 141(11):846–850

    PubMed  Google Scholar 

  141. Srinivasan V et al (2005) Melatonin, immune function and aging. Immun Ageing 2:17

    Article  PubMed  CAS  Google Scholar 

  142. Stanewsky R et al (1998) The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila. Cell 95(5):681–692

    Article  PubMed  CAS  Google Scholar 

  143. Sun Y et al (2006) MOP3, a component of the molecular clock, regulates the development of B cells. Immunology 119(4):451–460

    Article  PubMed  CAS  Google Scholar 

  144. Suzuki S et al (1997) Circadian rhythm of leucocytes and lymphocytes subsets and its possible correlation with the function of the autonomic nervous system. Clin Exp Immunol 110(3):500–508

    Article  PubMed  CAS  Google Scholar 

  145. Taheri S et al (2004) Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med 1(3):e62

    Article  PubMed  CAS  Google Scholar 

  146. Tasali E, Mokhlesi B, Van Cauter E (2008) Obstructive sleep apnea and type 2 diabetes: interacting epidemics. Chest 133(2):496–506

    Article  PubMed  Google Scholar 

  147. Tobler I, Borbely AA, Groos G (1983) The effect of sleep deprivation on sleep in rats with suprachiasmatic lesions. Neurosci Lett 42(1):49–54

    Article  PubMed  CAS  Google Scholar 

  148. Toh KL et al (2001) An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science 291(5506):1040–1043

    Article  PubMed  CAS  Google Scholar 

  149. Toth LA, Tolley EA, Krueger JM (1993) Sleep as a prognostic indicator during infectious disease in rabbits. Proc Soc Exp Biol Med 203(2):179–192

    PubMed  CAS  Google Scholar 

  150. Tucker MA et al (2006) A daytime nap containing solely non-REM sleep enhances declarative but not procedural memory. Neurobiol Learn Mem 86(2):241–247

    Article  PubMed  Google Scholar 

  151. Turek FW et al (2005) Obesity and metabolic syndrome in circadian Clock mutant mice. Science 308(5724):1043–1045

    Article  PubMed  CAS  Google Scholar 

  152. van der Horst GT et al (1999) Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature 398(6728):627–630

    Article  PubMed  Google Scholar 

  153. Van der Zee EA et al (2008) Circadian time–place learning in mice depends on Cry genes. Curr Biol 18(11):844–848

    Article  PubMed  CAS  Google Scholar 

  154. Vandewalle G et al (2009) Functional magnetic resonance imaging-assessed brain responses during an executive task depend on interaction of sleep homeostasis, circadian phase, and PER3 genotype. J Neurosci Off J Soc Neurosci 29(25):7948–7956

    Article  CAS  Google Scholar 

  155. Viola AU et al (2007) PER3 polymorphism predicts sleep structure and waking performance. Curr Biol 17(7):613–618

    Article  PubMed  CAS  Google Scholar 

  156. Vitaterna MH et al (1994) Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science 264(5159):719–725

    Article  PubMed  CAS  Google Scholar 

  157. Vitaterna MH et al (1999) Differential regulation of mammalian period genes and circadian rhythmicity by cryptochromes 1 and 2. Proc Natl Acad Sci USA 96(21):12114–12119

    Article  PubMed  CAS  Google Scholar 

  158. von Gall C et al (1998) CREB in the mouse SCN: a molecular interface coding the phase-adjusting stimuli light, glutamate, PACAP, and melatonin for clockwork access. J Neurosci 18(24):10389–10397

    Google Scholar 

  159. Wang LM et al (2005) Melatonin inhibits hippocampal long-term potentiation. Eur J Neurosci 22(9):2231–2237

    Article  PubMed  Google Scholar 

  160. Wang, LM et al. (2009) Expression of the circadian clock gene Period2 in the hippocampus: possible implications for synaptic plasticity and learned behaviour. ASN Neuro. 1(3):e00012

    Google Scholar 

  161. Wisor JP et al (2002) A role for cryptochromes in sleep regulation. BMC Neurosci 3:20

    Article  PubMed  Google Scholar 

  162. Wisor JP et al (2008) Sleep deprivation effects on circadian clock gene expression in the cerebral cortex parallel electroencephalographic differences among mouse strains. J Neurosci 28(28):7193–7201

    Article  PubMed  CAS  Google Scholar 

  163. Woon PY et al (2007) Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes. Proc Natl Acad Sci USA 104(36):14412–14417

    Article  PubMed  CAS  Google Scholar 

  164. Xu Y et al (2005) Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome. Nature 434(7033):640–644

    Article  PubMed  CAS  Google Scholar 

  165. Xu Y et al (2007) Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell 128(1):59–70

    Article  PubMed  CAS  Google Scholar 

  166. Yaffe K et al (2004) The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA 292(18):2237–2242

    Article  PubMed  CAS  Google Scholar 

  167. Yang S et al (2009) The role of mPer2 clock gene in glucocorticoid and feeding rhythms. Endocrinology 150(5):2153–2160

    Article  PubMed  CAS  Google Scholar 

  168. Yannielli PC et al (2007) Ghrelin effects on the circadian system of mice. J Neurosci 27(11):2890–2895

    Article  PubMed  CAS  Google Scholar 

  169. Yin JC et al (1995) CREB as a memory modulator: induced expression of a dCREB2 activator isoform enhances long-term memory in Drosophila. Cell 81(1):107–115

    Article  PubMed  CAS  Google Scholar 

  170. Youngblood BD et al (1999) The effects of paradoxical sleep deprivation and valine on spatial learning and brain 5-HT metabolism. Physiol Behav 67(5):643–649

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Johanna Barclay for critical reading of the manuscript. H.O. is an Emmy Noether fellow of the German Research Foundation (DFG). A.S. is supported by the Max Planck Society (MPG).

Author information

Authors and Affiliations

  1. Circadian Rhythms Group, Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077, Göttingen, Germany

    Dominic Landgraf, Anton Shostak & Henrik Oster

Authors
  1. Dominic Landgraf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anton Shostak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Henrik Oster
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Henrik Oster.

Additional information

D. Landgraf and A. Shostak contributed equally to this work.

This article is published as part of the Special Issue on Sleep.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Landgraf, D., Shostak, A. & Oster, H. Clock genes and sleep. Pflugers Arch - Eur J Physiol 463, 3–14 (2012). https://doi.org/10.1007/s00424-011-1003-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-011-1003-9

Keywords

Search

Navigation