Advertisement

Circadian rhythms and sleep—the metabolic connection

  • Urs AlbrechtEmail author
Invited Review

Abstract

The circadian system coordinates mammalian physiology and behavior with the environmental light–dark cycle. It allocates sleep to the inactivity phase using various mechanisms involving neurotransmitters, nuclear receptors, and protein kinases. These pathways are related to metabolism, indicating that the circadian system and sleep are connected via metabolic parameters. This suggests that organs other than the brain may “sleep.” A hypothetic view on this aspect is presented providing a different perspective on sleep regulation.

Keywords

Nuclear receptors Neurotransmitters Protein kinases Metabolism AMPK Cell death Apoptosis Adenosine ATP release Catecholamines cGMP Circadian rhythm Gene expression Liver Neuroendocrinology Protein kinase Sleep apnea 

Notes

Acknowledgments

I would like to thank Dr. Jürgen Ripperger for critical reading of the manuscript. U.A. is supported by the Swiss National Science foundation (SNF), the State of Fribourg, and the Japanese–Swiss Science and Technology Programme.

References

  1. 1.
    Ahnaou A, Drinkenburg WH (2011) Disruption of glycogen synthase kinase-3-beta activity leads to abnormalities in physiological measures in mice. Behav Brain Res 221(1):246–252. doi: 10.1016/j.bbr.2011.03.004 PubMedCrossRefGoogle Scholar
  2. 2.
    Appelbaum L, Wang G, Yokogawa T, Skariah GM, Smith SJ, Mourrain P, Mignot E (2010) Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons. Neuron 68(1):87–98. doi: 10.1016/j.neuron.2010.09.006 PubMedCrossRefGoogle Scholar
  3. 3.
    Arendt J, Bojkowski C, Franey C, Wright J, Marks V (1985) Immunoassay of 6-hydroxymelatonin sulfate in human plasma and urine: abolition of the urinary 24-hour rhythm with atenolol. J Clin Endocrinol Metab 60(6):1166–1173PubMedCrossRefGoogle Scholar
  4. 4.
    Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD (2004) The equilibrative nucleoside transporter family, SLC29. Pflugers Arch 447(5):735–743. doi: 10.1007/s00424-003-1103-2 PubMedCrossRefGoogle Scholar
  5. 5.
    Benedetti F, Bernasconi A, Lorenzi C, Pontiggia A, Serretti A, Colombo C, Smeraldi E (2004) A single nucleotide polymorphism in glycogen synthase kinase 3-beta promoter gene influences onset of illness in patients affected by bipolar disorder. Neurosci Lett 355(1–2):37–40PubMedCrossRefGoogle Scholar
  6. 6.
    Benington JH, Heller HC (1995) Restoration of brain energy metabolism as the function of sleep. Prog Neurobiol 45(4):347–360PubMedCrossRefGoogle Scholar
  7. 7.
    Bianchi G, Marchesini G, Nicolino F, Graziani R, Sgarbi D, Loguercio C, Abbiati R, Zoli M (2005) Psychological status and depression in patients with liver cirrhosis. Dig Liver Dis 37(8):593–600. doi: 10.1016/j.dld.2005.01.020 PubMedCrossRefGoogle Scholar
  8. 8.
    Boison D (2006) Adenosine kinase, epilepsy and stroke: mechanisms and therapies. Trends Pharmacol Sci 27(12):652–658. doi: 10.1016/j.tips.2006.10.008 PubMedCrossRefGoogle Scholar
  9. 9.
    Borbely AA (1998) Processes underlying sleep regulation. Horm Res 49(3–4):114–117PubMedGoogle Scholar
  10. 10.
    Canto C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J (2009) AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity. Nature 458(7241):1056–1060. doi: 10.1038/nature07813 PubMedCrossRefGoogle Scholar
  11. 11.
    Canto C, Jiang LQ, Deshmukh AS, Mataki C, Coste A, Lagouge M, Zierath JR, Auwerx J (2010) Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab 11(3):213–219. doi: 10.1016/j.cmet.2010.02.006 PubMedCrossRefGoogle Scholar
  12. 12.
    Chikahisa S, Fujiki N, Kitaoka K, Shimizu N, Sei H (2009) Central AMPK contributes to sleep homeostasis in mice. Neuropharmacology 57(4):369–374. doi: 10.1016/j.neuropharm.2009.07.015 PubMedCrossRefGoogle Scholar
  13. 13.
    Cirelli C, Gutierrez CM, Tononi G (2004) Extensive and divergent effects of sleep and wakefulness on brain gene expression. Neuron 41(1):35–43PubMedCrossRefGoogle Scholar
  14. 14.
    Cordoba J, Cabrera J, Lataif L, Penev P, Zee P, Blei AT (1998) High prevalence of sleep disturbance in cirrhosis. Hepatology 27(2):339–345. doi: 10.1002/hep.510270204 PubMedCrossRefGoogle Scholar
  15. 15.
    Cunha RA (2005) Neuroprotection by adenosine in the brain: from A(1) receptor activation to A (2A) receptor blockade. Purinergic Signal 1(2):111–134. doi: 10.1007/s11302-005-0649-1 PubMedCrossRefGoogle Scholar
  16. 16.
    Datta S, Desarnaud F (2010) Protein kinase A in the pedunculopontine tegmental nucleus of rat contributes to regulation of rapid eye movement sleep. J Neurosci 30(37):12263–12273. doi: 10.1523/JNEUROSCI.1563-10.2010 PubMedCrossRefGoogle Scholar
  17. 17.
    de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS 2nd, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95(1):322–327PubMedCrossRefGoogle Scholar
  18. 18.
    Diaz-Ruiz O, Navarro L, Mendez-Diaz M, Galicia O, Elder JH, Sanna PP, Drucker-Colin R, Prospero-Garcia O (2001) Inhibition of the ERK pathway prevents HIVgp120-induced REM sleep increase. Brain Res 913(1):78–81PubMedCrossRefGoogle Scholar
  19. 19.
    Donner N, Handa RJ (2009) Estrogen receptor beta regulates the expression of tryptophan-hydroxylase 2 mRNA within serotonergic neurons of the rat dorsal raphe nuclei. Neuroscience 163(2):705–718. doi: 10.1016/j.neuroscience.2009.06.046 PubMedCrossRefGoogle Scholar
  20. 20.
    Dudley CA, Erbel-Sieler C, Estill SJ, Reick M, Franken P, Pitts S, McKnight SL (2003) Altered patterns of sleep and behavioral adaptability in NPAS2-deficient mice. Science 301(5631):379–383. doi: 10.1126/science.1082795 PubMedCrossRefGoogle Scholar
  21. 21.
    Franken P, Dijk DJ (2009) Circadian clock genes and sleep homeostasis. Eur J Neurosci 29(9):1820–1829. doi: 10.1111/j.1460-9568.2009.06723.x PubMedCrossRefGoogle Scholar
  22. 22.
    Franken P, Dudley CA, Estill SJ, Barakat M, Thomason R, O'Hara BF, McKnight SL (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. doi: 10.1073/pnas.0602006103 PubMedCrossRefGoogle Scholar
  23. 23.
    Fukushima H, Maeda R, Suzuki R, Suzuki A, Nomoto M, Toyoda H, Wu LJ, Xu H, Zhao MG, Ueda K, Kitamoto A, Mamiya N, Yoshida T, Homma S, Masushige S, Zhuo M, Kida S (2008) Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory formation and rescues memory loss with aging. J Neurosci 28(40):9910–9919. doi: 10.1523/JNEUROSCI.2625-08.2008 PubMedCrossRefGoogle Scholar
  24. 24.
    Gery S, Virk RK, Chumakov K, Yu A, Koeffler HP (2007) The clock gene Per2 links the circadian system to the estrogen receptor. Oncogene 26(57):7916–7920. doi: 10.1038/sj.onc.1210585 PubMedCrossRefGoogle Scholar
  25. 25.
    Gottlieb DJ, O'Connor GT, Wilk JB (2007) Genome-wide association of sleep and circadian phenotypes. BMC Med Genet 8(Suppl 1):S9. doi: 10.1186/1471-2350-8-S1-S9 PubMedCrossRefGoogle Scholar
  26. 26.
    Grady SP, Nishino S, Czeisler CA, Hepner D, Scammell TE (2006) Diurnal variation in CSF orexin-A in healthy male subjects. Sleep 29(3):295–297PubMedGoogle Scholar
  27. 27.
    Green CB, Takahashi JS, Bass J (2008) The meter of metabolism. Cell 134(5):728–742. doi: 10.1016/j.cell.2008.08.022 PubMedCrossRefGoogle Scholar
  28. 28.
    Hampp G, Ripperger JA, Houben T, Schmutz I, Blex C, Perreau-Lenz S, Brunk I, Spanagel R, Ahnert-Hilger G, Meijer JH, Albrecht U (2008) Regulation of monoamine oxidase A by circadian-clock components implies clock influence on mood. Curr Biol 18(9):678–683. doi: 10.1016/j.cub.2008.04.012 PubMedCrossRefGoogle Scholar
  29. 29.
    Haque R, Ali FG, Biscoglia R, Abey J, Weller J, Klein D, Iuvone PM (2010) CLOCK and NPAS2 have overlapping roles in the circadian oscillation of arylalkylamine N-acetyltransferase mRNA in chicken cone photoreceptors. J Neurochem 113(5):1296–1306. doi: 10.1111/j.1471-4159.2010.06698.x PubMedGoogle Scholar
  30. 30.
    Hellman K, Hernandez P, Park A, Abel T (2010) Genetic evidence for a role for protein kinase A in the maintenance of sleep and thalamocortical oscillations. Sleep 33(1):19–28PubMedGoogle Scholar
  31. 31.
    Hirota T, Fukada Y (2004) Resetting mechanism of central and peripheral circadian clocks in mammals. Zoolog Sci 21(4):359–368PubMedCrossRefGoogle Scholar
  32. 32.
    Ho AK, Chik CL (2010) Modulation of Aanat gene transcription in the rat pineal gland. J Neurochem 112(2):321–331. doi: 10.1111/j.1471-4159.2009.06457.x PubMedCrossRefGoogle Scholar
  33. 33.
    Ibata K, Sun Q, Turrigiano GG (2008) Rapid synaptic scaling induced by changes in postsynaptic firing. Neuron 57(6):819–826. doi: 10.1016/j.neuron.2008.02.031 PubMedCrossRefGoogle Scholar
  34. 34.
    Jepson JB, Zaltzman P, Udenfriend S (1962) Microsomal hydroxylation of tryptamine, indoleacetic acid and related compounds, to 6-hydroxy derivatives. Biochim Biophys Acta 62:91–102PubMedCrossRefGoogle Scholar
  35. 35.
    Jin X, Shearman LP, Weaver DR, Zylka MJ, de Vries GJ, Reppert SM (1999) A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. Cell 96(1):57–68PubMedCrossRefGoogle Scholar
  36. 36.
    Kalinchuk AV, Lu Y, Stenberg D, Rosenberg PA, Porkka-Heiskanen T (2006) Nitric oxide production in the basal forebrain is required for recovery sleep. J Neurochem 99(2):483–498. doi: 10.1111/j.1471-4159.2006.04077.x PubMedCrossRefGoogle Scholar
  37. 37.
    Kim KS, Kim CH, Hwang DY, Seo H, Chung S, Hong SJ, Lim JK, Anderson T, Isacson O (2003) Orphan nuclear receptor Nurr1 directly transactivates the promoter activity of the tyrosine hydroxylase gene in a cell-specific manner. J Neurochem 85(3):622–634PubMedCrossRefGoogle Scholar
  38. 38.
    Kim TD, Woo KC, Cho S, Ha DC, Jang SK, Kim KT (2007) Rhythmic control of AANAT translation by hnRNP Q in circadian melatonin production. Genes Dev 21(7):797–810. doi: 10.1101/gad.1519507 PubMedCrossRefGoogle Scholar
  39. 39.
    Kopp C, Albrecht U, Zheng B, Tobler I (2002) Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant mice. Eur J Neurosci 16(6):1099–1106PubMedCrossRefGoogle Scholar
  40. 40.
    Krezel W, Ghyselinck N, Samad TA, Dupe V, Kastner P, Borrelli E, Chambon P (1998) Impaired locomotion and dopamine signaling in retinoid receptor mutant mice. Science 279(5352):863–867PubMedCrossRefGoogle Scholar
  41. 41.
    Lamia KA, Sachdeva UM, DiTacchio L, Williams EC, Alvarez JG, Egan DF, Vasquez DS, Juguilon H, Panda S, Shaw RJ, Thompson CB, Evans RM (2009) AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 326(5951):437–440. doi: 10.1126/science.1172156 PubMedCrossRefGoogle Scholar
  42. 42.
    Lammi J, Perlmann T, Aarnisalo P (2008) Corepressor interaction differentiates the permissive and non-permissive retinoid X receptor heterodimers. Arch Biochem Biophys 472(2):105–114. doi: 10.1016/j.abb.2008.02.003 PubMedCrossRefGoogle Scholar
  43. 43.
    Langmesser S, Franken P, Feil S, Emmenegger Y, Albrecht U, Feil R (2009) cGMP-dependent protein kinase type I is implicated in the regulation of the timing and quality of sleep and wakefulness. PLoS One 4(1):e4238. doi: 10.1371/journal.pone.0004238 PubMedCrossRefGoogle Scholar
  44. 44.
    Laposky A, Easton A, Dugovic C, Walisser J, Bradfield C, Turek F (2005) Deletion of the mammalian circadian clock gene BMAL1/Mop3 alters baseline sleep architecture and the response to sleep deprivation. Sleep 28(4):395–409PubMedGoogle Scholar
  45. 45.
    Lehninger AL (1977) Biochemistry, 2nd edn. Worth, New YorkGoogle Scholar
  46. 46.
    Maret S, Franken P, Dauvilliers Y, Ghyselinck NB, Chambon P, Tafti M (2005) Retinoic acid signaling affects cortical synchrony during sleep. Science 310(5745):111–113. doi: 10.1126/science.1117623 PubMedCrossRefGoogle Scholar
  47. 47.
    Marston OJ, Williams RH, Canal MM, Samuels RE, Upton N, Piggins HD (2008) Circadian and dark-pulse activation of orexin/hypocretin neurons. Mol Brain 1:19. doi: 10.1186/1756-6606-1-19 PubMedCrossRefGoogle Scholar
  48. 48.
    Mathews II, Erion MD, Ealick SE (1998) Structure of human adenosine kinase at 1.5 A resolution. Biochemistry 37(45):15607–15620. doi: 10.1021/bi9815445.bi9815445 PubMedCrossRefGoogle Scholar
  49. 49.
    Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY (2009) Sleep and circadian abnormalities in patients with cirrhosis: features of delayed sleep phase syndrome? Metab Brain Dis 24(3):427–439. doi: 10.1007/s11011-009-9146-5 PubMedCrossRefGoogle Scholar
  50. 50.
    Nestler EJ, Carlezon WA Jr (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59(12):1151–1159. doi: 10.1016/j.biopsych.2005.09.018 PubMedCrossRefGoogle Scholar
  51. 51.
    Oster H, Werner C, Magnone MC, Mayser H, Feil R, Seeliger MW, Hofmann F, Albrecht U (2003) cGMP-dependent protein kinase II modulates mPer1 and mPer2 gene induction and influences phase shifts of the circadian clock. Curr Biol 13(9):725–733PubMedCrossRefGoogle Scholar
  52. 52.
    Palchykova S, Winsky-Sommerer R, Shen HY, Boison D, Gerling A, Tobler I (2010) Manipulation of adenosine kinase affects sleep regulation in mice. J Neurosci 30(39):13157–13165. doi: 10.1523/JNEUROSCI.1359-10.2010 PubMedCrossRefGoogle Scholar
  53. 53.
    Perlmann T, Jansson L (1995) A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1. Genes Dev 9(7):769–782PubMedCrossRefGoogle Scholar
  54. 54.
    Porkka-Heiskanen T, Alanko L, Kalinchuk A, Stenberg D (2002) Adenosine and sleep. Sleep Med Rev 6(4):321–332PubMedCrossRefGoogle Scholar
  55. 55.
    Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U, Schibler U (2002) The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110(2):251–260PubMedCrossRefGoogle Scholar
  56. 56.
    Radulovacki M (1985) Role of adenosine in sleep in rats. Rev Clin Basic Pharm 5(3–4):327–339PubMedGoogle Scholar
  57. 57.
    Raizen DM, Zimmerman JE, Maycock MH, Ta UD, You YJ, Sundaram MV, Pack AI (2008) Lethargus is a Caenorhabditis elegans sleep-like state. Nature 451(7178):569–572. doi: 10.1038/nature06535 PubMedCrossRefGoogle Scholar
  58. 58.
    Ripperger JA, Jud C, Albrecht U (2011) The daily rhythm of mice. FEBS Lett. doi: 10.1016/j.febslet.2011.02.027
  59. 59.
    Ripperger JA, Schmutz I, Albrecht U (2010) PERsuading nuclear receptors to dance the circadian rhythm. Cell Cycle 9(13):2513–2519CrossRefGoogle Scholar
  60. 60.
    Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92(4):573–585PubMedCrossRefGoogle Scholar
  61. 61.
    Salomon RM, Ripley B, Kennedy JS, Johnson B, Schmidt D, Zeitzer JM, Nishino S, Mignot E (2003) Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects. Biol Psychiatry 54(2):96–104PubMedCrossRefGoogle Scholar
  62. 62.
    Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE (2010) Sleep state switching. Neuron 68(6):1023–1042. doi: 10.1016/j.neuron.2010.11.032 PubMedCrossRefGoogle Scholar
  63. 63.
    Schmutz I, Ripperger JA, Baeriswyl-Aebischer S, Albrecht U (2010) The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors. Genes Dev 24(4):345–357. doi: 10.1101/gad.564110 PubMedCrossRefGoogle Scholar
  64. 64.
    Schwiebert EM, Zsembery A (2003) Extracellular ATP as a signaling molecule for epithelial cells. Biochim Biophys Acta 1615(1–2):7–32PubMedGoogle Scholar
  65. 65.
    Sei H (2008) Vitamin A and sleep regulation. J Med Invest 55(1–2):1–8PubMedCrossRefGoogle Scholar
  66. 66.
    Shostak A, Landgraf D, Oster H (2011) Clock genes and sleep. Pflugers Arch-Eur J Physiol (in press)Google Scholar
  67. 67.
    Steenland HW, Wu V, Fukushima H, Kida S, Zhuo M (2010) CaMKIV over-expression boosts cortical 4–7 Hz oscillations during learning and 1–4 Hz delta oscillations during sleep. Mol Brain 3:16. doi: 10.1186/1756-6606-3-16 PubMedCrossRefGoogle Scholar
  68. 68.
    Steindl PE, Ferenci P, Marktl W (1997) Impaired hepatic catabolism of melatonin in cirrhosis. Ann Intern Med 127(6):494PubMedGoogle Scholar
  69. 69.
    Steindl PE, Finn B, Bendok B, Rothke S, Zee PC, Blei AT (1995) Disruption of the diurnal rhythm of plasma melatonin in cirrhosis. Ann Intern Med 123(4):274–277PubMedGoogle Scholar
  70. 70.
    Strecker RE, Morairty S, Thakkar MM, Porkka-Heiskanen T, Basheer R, Dauphin LJ, Rainnie DG, Portas CM, Greene RW, McCarley RW (2000) Adenosinergic modulation of basal forebrain and preoptic/anterior hypothalamic neuronal activity in the control of behavioral state. Behav Brain Res 115(2):183–204PubMedCrossRefGoogle Scholar
  71. 71.
    Sullivan SS, Guilleminault C (2009) Emerging drugs for insomnia: new frontiers for old and novel targets. Expert Opin Emerg Drugs 14(3):411–422. doi: 10.1517/14728210903171948 PubMedCrossRefGoogle Scholar
  72. 72.
    Taheri S, Sunter D, Dakin C, Moyes S, Seal L, Gardiner J, Rossi M, Ghatei M, Bloom S (2000) Diurnal variation in orexin A immunoreactivity and prepro-orexin mRNA in the rat central nervous system. Neurosci Lett 279(2):109–112PubMedCrossRefGoogle Scholar
  73. 73.
    Tanaka S, Kodama T, Nonaka T, Toyoda H, Arai M, Fukazawa M, Honda Y, Honda M, Mignot E (2010) Transcriptional regulation of the hypocretin/orexin gene by NR6A1. Biochem Biophys Res Commun 403(2):178–183. doi: 10.1016/j.bbrc.2010.11.001 PubMedCrossRefGoogle Scholar
  74. 74.
    Um JH, Pendergast JS, Springer DA, Foretz M, Viollet B, Brown A, Kim MK, Yamazaki S, Chung JH (2011) AMPK regulates circadian rhythms in a tissue- and isoform-specific manner. PLoS One 6(3):e18450. doi: 10.1371/journal.pone.0018450 PubMedCrossRefGoogle Scholar
  75. 75.
    Um JH, Yang S, Yamazaki S, Kang H, Viollet B, Foretz M, Chung JH (2007) Activation of 5′-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2. J Biol Chem 282(29):20794–20798. doi: 10.1074/jbc.C700070200 PubMedCrossRefGoogle Scholar
  76. 76.
    Vanselow K, Kramer A (2007) Role of phosphorylation in the mammalian circadian clock. Cold Spring Harb Symp Quant Biol 72:167–176. doi: 10.1101/sqb.2007.72.036 PubMedCrossRefGoogle Scholar
  77. 77.
    Vyazovskiy VV, Olcese U, Hanlon EC, Nir Y, Cirelli C, Tononi G (2011) Local sleep in awake rats. Nature 472(7344):443–447. doi: 10.1038/nature10009 PubMedCrossRefGoogle Scholar
  78. 78.
    Wei F, Qiu CS, Liauw J, Robinson DA, Ho N, Chatila T, Zhuo M (2002) Calcium calmodulin-dependent protein kinase IV is required for fear memory. Nat Neurosci 5(6):573–579. doi: 10.1038/nn855 PubMedCrossRefGoogle Scholar
  79. 79.
    Wisor JP, O'Hara BF, Terao A, Selby CP, Kilduff TS, Sancar A, Edgar DM, Franken P (2002) A role for cryptochromes in sleep regulation. BMC Neurosci 3:20PubMedCrossRefGoogle Scholar
  80. 80.
    Xu Y, Padiath QS, Shapiro RE, Jones CR, Wu SC, Saigoh N, Saigoh K, Ptacek LJ, Fu YH (2005) Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome. Nature 434(7033):640–644. doi: 10.1038/nature03453 PubMedCrossRefGoogle Scholar
  81. 81.
    Yin L, Wang J, Klein PS, Lazar MA (2006) Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock. Science 311(5763):1002–1005. doi: 10.1126/science.1121613 PubMedCrossRefGoogle Scholar
  82. 82.
    Yin L, Wu N, Curtin JC, Qatanani M, Szwergold NR, Reid RA, Waitt GM, Parks DJ, Pearce KH, Wisely GB, Lazar MA (2007) Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways. Science 318(5857):1786–1789. doi: 10.1126/science.1150179 PubMedCrossRefGoogle Scholar
  83. 83.
    Zhang J, Kaasik K, Blackburn MR, Lee CC (2006) Constant darkness is a circadian metabolic signal in mammals. Nature 439(7074):340–343. doi: 10.1038/nature04368 PubMedCrossRefGoogle Scholar
  84. 84.
    Zhang X, Beaulieu JM, Sotnikova TD, Gainetdinov RR, Caron MG (2004) Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science 305(5681):217. doi: 10.1126/science.1097540.305/5681/217 PubMedCrossRefGoogle Scholar
  85. 85.
    Zimmermann H (2000) Extracellular metabolism of ATP and other nucleotides. Naunyn Schmiedebergs Arch Pharmacol 362(4–5):299–309PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of Biology, Unit of BiochemistryUniversity of FribourgFribourgSwitzerland

Personalised recommendations