A metabolic–transcriptional network links sleep and cellular energetics in the brain

Invited Review

Abstract

This review proposes a mechanistic link between cellular metabolic status, transcriptional regulatory changes and sleep. Sleep loss is associated with changes in cellular metabolic status in the brain. Metabolic sensors responsive to cellular metabolic status regulate the circadian clock transcriptional network. Modifications of the transcriptional activity of circadian clock genes affect sleep/wake state changes. Changes in sleep state reverse sleep loss-induced changes in cellular metabolic status. It is thus proposed that the regulation of circadian clock genes by cellular metabolic sensors is a critical intermediate step in the link between cellular metabolic status and sleep. Studies of this regulatory relationship may offer insights into the function of sleep at the cellular level.

Keywords

Nicotinamide adenine dinucleotide Adenosine triphosphate Slow wave activity Sleep Circadian Adenosine monophosphate-activated protein kinase Glycogen Sirtuin Poly(ADP)ribosyl polymerase Peroxisome proliferator-activated receptor 

Abbreviations

NREMS

Non-rapid eye movement sleep

SWA

Slow wave activity

EEG

Electroencephalographic/electroencephalogram

ATP

Adenosine triphosphate

ADP

Adenosine diphosphate

AMP

Adenosine monophosphate

AMPK

Adenosine monophosphate-activated protein kinase

cry

Cryptochrome

per

Period

NAD

Nicotine adenine dinucleotide

HDAC

Histone deacetylase

PARP

Poly ADP-ribose polymerase

GSK3b

Glycogen synthase kinase 3b

PPARs

Peroxisome proliferator-activated receptors

References

  1. 1.
    Achermann P, Borbely AA (1997) Low-frequency (<1 Hz) oscillations in the human sleep electroencephalogram. Neuroscience 81:213–222PubMedCrossRefGoogle Scholar
  2. 2.
    Ahnaou A, Drinkenburg WH (2010) Disruption of glycogen synthase kinase-3-beta activity leads to abnormalities in physiological measures in mice. Behav Brain Res 221:246–252CrossRefGoogle Scholar
  3. 3.
    Alcain FJ, Villalba JM (2009) Sirtuin inhibitors. Expert Opin Ther Pat 19:283–294PubMedCrossRefGoogle Scholar
  4. 4.
    Alle H, Roth A, Geiger JR (2009) Energy-efficient action potentials in hippocampal mossy fibers. Science 325:1405–1408PubMedCrossRefGoogle Scholar
  5. 5.
    Asher G, Schibler U (2011) Crosstalk between components of circadian and metabolic cycles in mammals. Cell Metab 13:125–137PubMedCrossRefGoogle Scholar
  6. 6.
    Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, Mostoslavsky R, Alt FW, Schibler U (2008) SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134:317–328PubMedCrossRefGoogle Scholar
  7. 7.
    Asher G, Reinke H, Altmeyer M, Gutierrez-Arcelus M, Hottiger MO, Schibler U (2010) Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding. Cell 142:943–953PubMedCrossRefGoogle Scholar
  8. 8.
    Attwell D, Laughlin SB (2001) An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 21:1133–1145PubMedCrossRefGoogle Scholar
  9. 9.
    Bechtold DA (2008) Energy-responsive timekeeping. J Genet 87:447–458PubMedCrossRefGoogle Scholar
  10. 10.
    Benington JH, Heller HC (1995) Restoration of brain energy metabolism as the function of sleep. Prog Neurobiol 45:347–360PubMedCrossRefGoogle Scholar
  11. 11.
    Boger DL, Henriksen SJ, Cravatt BF (1998) Oleamide: an endogenous sleep-inducing lipid and prototypical member of a new class of biological signaling molecules. Curr Pharm Des 4:303–314PubMedGoogle Scholar
  12. 12.
    Borbely AA, Achermann P (2004) Sleep homeostasis and models of sleep regulation. In: Kryger MH, Roth T, Dement WC (eds) Principles and practice of sleep medicine. Saunders, Philadelphia, pp 377–390Google Scholar
  13. 13.
    Bouaboula M, Hilairet S, Marchand J, Fajas L, Le Fur G, Casellas P (2005) Anandamide induced PPARgamma transcriptional activation and 3T3-L1 preadipocyte differentiation. Eur J Pharmacol 517:174–181PubMedCrossRefGoogle Scholar
  14. 14.
    Buchsbaum MS, Gillin JC, Wu J, Hazlett E, Sicotte N, Dupont RM, Bunney WE Jr (1989) Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography. Life Sci 45:1349–1356PubMedCrossRefGoogle Scholar
  15. 15.
    Buzsaki G, Kaila K, Raichle M (2007) Inhibition and brain work. Neuron 56:771–783PubMedCrossRefGoogle Scholar
  16. 16.
    Canaple L, Rambaud J, Dkhissi-Benyahya O, Rayet B, Tan NS, Michalik L, Delaunay F, Wahli W, Laudet V (2006) Reciprocal regulation of brain and muscle Arnt-like protein 1 and peroxisome proliferator-activated receptor alpha defines a novel positive feedback loop in the rodent liver circadian clock. Mol Endocrinol 20:1715–1727PubMedCrossRefGoogle Scholar
  17. 17.
    Chikahisa S, Tominaga K, Kawai T, Kitaoka K, Oishi K, Ishida N, Rokutan K, Sei H (2008) Bezafibrate, a PPARs agonist, decreases body temperature and enhances EEG delta oscillation during sleep in mice. Endocrinology 149:5262–5271PubMedCrossRefGoogle Scholar
  18. 18.
    Chikahisa S, Fujiki N, Kitaoka K, Shimizu N, Sei H (2009) Central AMPK contributes to sleep homeostasis in mice. Neuropharmacology 57:369–374PubMedCrossRefGoogle Scholar
  19. 19.
    Cirelli C (2006) Cellular consequences of sleep deprivation in the brain. Sleep Med Rev 10:307–321PubMedCrossRefGoogle Scholar
  20. 20.
    Cirelli C, Tononi G (1998) Differences in gene expression between sleep and waking as revealed by mRNA differential display. Brain Res Mol Brain Res 56:293–305PubMedCrossRefGoogle Scholar
  21. 21.
    Cravatt BF, Prospero-Garcia O, Siuzdak G, Gilula NB, Henriksen SJ, Boger DL, Lerner RA (1995) Chemical characterization of a family of brain lipids that induce sleep. Science 268:1506–1509PubMedCrossRefGoogle Scholar
  22. 22.
    Dauvilliers Y, Tafti M (2008) The genetic basis of sleep disorders. Curr Pharm Des 14:3386–3395PubMedCrossRefGoogle Scholar
  23. 23.
    DeBruyne JP, Noton E, Lambert CM, Maywood ES, Weaver DR, Reppert SM (2006) A clock shock: mouse CLOCK is not required for circadian oscillator function. Neuron 50:465PubMedCrossRefGoogle Scholar
  24. 24.
    Destexhe A, Contreras D, Steriade M (1999) Spatiotemporal analysis of local field potentials and unit discharges in cat cerebral cortex during natural wake and sleep states. J Neurosci 19:4595–4608PubMedGoogle Scholar
  25. 25.
    Dworak M, McCarley RW, Kim T, Kalinchuk AV, Basheer R (2010) Sleep and brain energy levels: ATP changes during sleep. J Neurosci 30:9007–9016PubMedCrossRefGoogle Scholar
  26. 26.
    Etchegaray JP, Machida KK, Noton E, Constance CM, Dallmann R, Di Napoli MN, DeBruyne JP, Lambert CM, Yu EA, Reppert SM, Weaver DR (2009) Casein kinase 1 delta regulates the pace of the mammalian circadian clock. Mol Cell Biol 29:3853–3866PubMedCrossRefGoogle Scholar
  27. 27.
    Franken P, Dijk DJ (2009) Circadian clock genes and sleep homeostasis. Eur J Neurosci 29:1820–1829PubMedCrossRefGoogle Scholar
  28. 28.
    Franken P, Thomason R, Heller HC, O'Hara BF (2007) A non-circadian role for clock-genes in sleep homeostasis: a strain comparison. BMC Neurosci 8:87PubMedCrossRefGoogle Scholar
  29. 29.
    Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodriguez De Fonseca F, Rosengarth A, Luecke H, Di Giacomo B, Tarzia G, Piomelli D (2003) Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 425:90–93PubMedCrossRefGoogle Scholar
  30. 30.
    Gamble KL, Allen GC, Zhou T, McMahon DG (2007) Gastrin-releasing peptide mediates light-like resetting of the suprachiasmatic nucleus circadian pacemaker through cAMP response element-binding protein and Per1 activation. J Neurosci 27:12078–12087PubMedCrossRefGoogle Scholar
  31. 31.
    Haque R, Ali FG, Biscoglia R, Abey J, Weller J, Klein D, Iuvone PM (2011) CLOCK and NPAS2 have overlapping roles in the circadian oscillation of arylalkylamine N-acetyltransferase mRNA in chicken cone photoreceptors. J Neurochem 113:1296–1306Google Scholar
  32. 32.
    Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774–785PubMedCrossRefGoogle Scholar
  33. 33.
    Hassa PO, Haenni SS, Elser M, Hottiger MO (2006) Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? Microbiol Mol Biol Rev 70:789–829PubMedCrossRefGoogle Scholar
  34. 34.
    He Y, Jones CR, Fujiki N, Xu Y, Guo B, Holder JL Jr, Rossner MJ, Nishino S, Fu YH (2009) The transcriptional repressor DEC2 regulates sleep length in mammals. Science 325:866–870PubMedCrossRefGoogle Scholar
  35. 35.
    Heiss WD, Pawlik G, Herholz K, Wagner R, Wienhard K (1985) Regional cerebral glucose metabolism in man during wakefulness, sleep, and dreaming. Brain Res 327:362–366PubMedCrossRefGoogle Scholar
  36. 36.
    Hirayama J, Sahar S, Grimaldi B, Tamaru T, Takamatsu K, Nakahata Y, Sassone-Corsi P (2007) CLOCK-mediated acetylation of BMAL1 controls circadian function. Nature 450:1086–1090PubMedCrossRefGoogle Scholar
  37. 37.
    Hong HK, Chong JL, Song W, Song EJ, Jyawook AA, Schook AC, Ko CH, Takahashi JS (2007) Inducible and reversible Clock gene expression in brain using the tTA system for the study of circadian behavior. PLoS Genet 3:e33PubMedCrossRefGoogle Scholar
  38. 38.
    Hottiger MO, Boothby M, Koch-Nolte F, Luscher B, Martin NM, Plummer R, Wang ZQ, Ziegler M (2011) Progress in the function and regulation of ADP-ribosylation. Sci Signal 4:mr5PubMedCrossRefGoogle Scholar
  39. 39.
    Huang W, Ramsey KM, Marcheva B, Bass J (2011) Circadian rhythms, sleep, and metabolism. J Clin Invest 121:2133–2141PubMedCrossRefGoogle Scholar
  40. 40.
    Iitaka C, Miyazaki K, Akaike T, Ishida N (2005) A role for glycogen synthase kinase-3beta in the mammalian circadian clock. J Biol Chem 280:29397–29402PubMedCrossRefGoogle Scholar
  41. 41.
    Johnson LA, Euston DR, Tatsuno M, McNaughton BL (2008) Stored-trace reactivation in rat prefrontal cortex is correlated with down-to-up state fluctuation density. J Neurosci 30:2650–2661CrossRefGoogle Scholar
  42. 42.
    Jones BE (2004) Activity, modulation and role of basal forebrain cholinergic neurons innervating the cerebral cortex. Prog Brain Res 145:157–169PubMedCrossRefGoogle Scholar
  43. 43.
    Karnovsky ML, Reich P, Anchors JM, Burrows BL (1983) Changes in brain glycogen during slow-wave sleep in the rat. J Neurochem 41:1498–1501PubMedCrossRefGoogle Scholar
  44. 44.
    Kennedy C, Gillin JC, Mendelson W, Suda S, Miyaoka M, Ito M, Nakamura RK, Storch FI, Pettigrew K, Mishkin M, Sokoloff L (1982) Local cerebral glucose utilization in non-rapid eye movement sleep. Nature 297:325–327PubMedCrossRefGoogle Scholar
  45. 45.
    Koethe D, Schreiber D, Giuffrida A, Mauss C, Faulhaber J, Heydenreich B, Hellmich M, Graf R, Klosterkotter J, Piomelli D, Leweke FM (2009) Sleep deprivation increases oleoylethanolamide in human cerebrospinal fluid. J Neural Transm 116:301–305PubMedCrossRefGoogle Scholar
  46. 46.
    Krishnakumar R, Kraus WL The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets. Mol Cell 39:8–24Google Scholar
  47. 47.
    Krueger JM, Rector DM, Roy S, Van Dongen HP, Belenky G, Panksepp J (2008) Sleep as a fundamental property of neuronal assemblies. Nat Rev Neurosci 9:910–919PubMedCrossRefGoogle Scholar
  48. 48.
    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 326:437–440PubMedCrossRefGoogle Scholar
  49. 49.
    Landgraf D, Shostak A, Oster H (2011) Clock genes and sleep. Pfluger's Archives Euro J Physiol, in press.Google Scholar
  50. 50.
    Mackiewicz M, Shockley KR, Romer MA, Galante RJ, Zimmerman JE, Naidoo N, Baldwin DA, Jensen ST, Churchill GA, Pack AI (2007) Macromolecule biosynthesis: a key function of sleep. Physiol Genomics 31:441–457PubMedCrossRefGoogle Scholar
  51. 51.
    Maquet P (1995) Sleep function(s) and cerebral metabolism. Behav Brain Res 69:75–83PubMedCrossRefGoogle Scholar
  52. 52.
    Maquet P, Dive D, Salmon E, Sadzot B, Franco G, Poirrier R, von Frenckell R, Franck G (1990) Cerebral glucose utilization during sleep–wake cycle in man determined by positron emission tomography and [18F]2-fluoro-2-deoxy-d-glucose method. Brain Res 513:136–143PubMedCrossRefGoogle Scholar
  53. 53.
    Martinek S, Inonog S, Manoukian AS, Young MW (2001) A role for the segment polarity gene shaggy/GSK-3 in the Drosophila circadian clock. Cell 105:769–779PubMedCrossRefGoogle Scholar
  54. 54.
    McMurry J, Castellion ME (1976) The generation of biochemical energy, organic and biological chemistry. Prentice-Hall, Upper Saddle River, NJ, pp 590–619Google Scholar
  55. 55.
    Morgenthaler FD, Lanz BR, Petit JM, Frenkel H, Magistretti PJ, Gruetter R (2009) Alteration of brain glycogen turnover in the conscious rat after 5 h of prolonged wakefulness. Neurochem Int 55:45–51PubMedCrossRefGoogle Scholar
  56. 56.
    Mukovski M, Chauvette S, Timofeev I, Volgushev M (2007) Detection of active and silent states in neocortical neurons from the field potential signal during slow-wave sleep. Cereb Cortex 17:400–414PubMedCrossRefGoogle Scholar
  57. 57.
    Naylor E, Aillon DV, Gabbert S, Harmon H, Johnson DA, Wilson GS, Petillo PA (2011) Real-time measurement of EEG/EMG and l-glutamate in mice: a biosensor study of neuronal activity during sleep. J Electroanal Chem 656:106–113CrossRefGoogle Scholar
  58. 58.
    Nelson DL, Cox MM (2008) Bioenergetics and biochemical reaction types. Lehninger principles of biochemistry. Freeman, New York, pp 485–519Google Scholar
  59. 59.
    Nelson DL, Cox MM (2008) The citric acid cycle. Lehninger principles of biochemistry. Freeman, New York, pp 615–646Google Scholar
  60. 60.
    Nelson DL, Cox MM (2008) Principles of metabolic regulation. Lehninger principles of biochemistry. Freeman, New York, pp 569–614Google Scholar
  61. 61.
    Nir Y, Staba RJ, Andrillon T, Vyazovskiy VV, Cirelli C, Fried I, Tononi G (2011) Regional slow waves and spindles in human sleep. Neuron 70:153–169PubMedCrossRefGoogle Scholar
  62. 62.
    Nonaka K, Nakazawa Y, Kotorii T (1983) Effects of antibiotics, minocycline and ampicillin, on human sleep. Brain Res 288:253–259PubMedCrossRefGoogle Scholar
  63. 63.
    Oishi K, Miyazaki K, Kadota K, Kikuno R, Nagase T, Atsumi G, Ohkura N, Azama T, Mesaki M, Yukimasa S, Kobayashi H, Iitaka C, Umehara T, Horikoshi M, Kudo T, Shimizu Y, Yano M, Monden M, Machida K, Matsuda J, Horie S, Todo T, Ishida N (2003) Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes. J Biol Chem 278:41519–41527PubMedCrossRefGoogle Scholar
  64. 64.
    Panda S, Antoch MP, Miller BH, Su AI, Schook AB, Straume M, Schultz PG, Kay SA, Takahashi JS, Hogenesch JB (2002) Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109:307–320PubMedCrossRefGoogle Scholar
  65. 65.
    Panossian L, Fenik P, Zhu Y, Zhan G, McBurney MW, Veasey S (2010) SIRT1 regulation of wakefulness and senescence-like phenotype in wake neurons. J Neurosci 31:4025–4036CrossRefGoogle Scholar
  66. 66.
    Petit JM, Tobler I, Kopp C, Morgenthaler F, Borbely AA, Magistretti PJ (2010) Metabolic response of the cerebral cortex following gentle sleep deprivation and modafinil administration. Sleep 33:901–908PubMedGoogle Scholar
  67. 67.
    Raizen DM, Wu MN (2010) Genome-wide association studies of sleep disorders. Chest 139:446–452CrossRefGoogle Scholar
  68. 68.
    Ramanathan L, Hu S, Frautschy SA, Siegel JM (2010) Short-term total sleep deprivation in the rat increases antioxidant responses in multiple brain regions without impairing spontaneous alternation behavior. Behav Brain Res 207:305–309PubMedCrossRefGoogle Scholar
  69. 69.
    Rector DM (2010) Local functional state differences between rat cortical columns. Curr Topics Med Chem, in pressGoogle Scholar
  70. 70.
    Rutter J, Reick M, Wu LC, McKnight SL (2001) Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science 293:510–514PubMedCrossRefGoogle Scholar
  71. 71.
    Scharf MT, Naidoo N, Zimmerman JE, Pack AI (2008) The energy hypothesis of sleep revisited. Prog Neurobiol 86:264–280PubMedCrossRefGoogle Scholar
  72. 72.
    Siegel JM (2011) REM sleep: a biological and psychological paradox. Sleep Med 15:139–142CrossRefGoogle Scholar
  73. 73.
    Silva RH, Abilio VC, Takatsu AL, Kameda SR, Grassl C, Chehin AB, Medrano WA, Calzavara MB, Registro S, Andersen ML, Machado RB, Carvalho RC, Ribeiro Rde A, Tufik S, Frussa-Filho R (2004) Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Neuropharmacology 46:895–903PubMedCrossRefGoogle Scholar
  74. 74.
    Smith SA (2002) Peroxisome proliferator-activated receptors and the regulation of mammalian lipid metabolism. Biochem Soc Trans 30:1086–1090PubMedCrossRefGoogle Scholar
  75. 75.
    Szymusiak R (2010) Hypothalamic versus neocortical control of sleep. Curr Opin Pulm Med 16:530–535PubMedCrossRefGoogle Scholar
  76. 76.
    Thakkar M, Mallick BN (1993) Rapid eye movement sleep-deprivation-induced changes in glucose metabolic enzymes in rat brain. Sleep 16:691–694PubMedGoogle Scholar
  77. 77.
    Tu BP, McKnight SL (2006) Metabolic cycles as an underlying basis of biological oscillations. Nat Rev Mol Cell Biol 7:696–701PubMedCrossRefGoogle Scholar
  78. 78.
    Van den Noort S, Brine K (1970) Effect of sleep on brain labile phosphates and metabolic rate. Am J Physiol 218:1434–1439PubMedGoogle Scholar
  79. 79.
    Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg RA (2001) hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 107:149–159PubMedCrossRefGoogle Scholar
  80. 80.
    Vyazovskiy VV, Cirelli C, Pfister-Genskow M, Faraguna U, Tononi G (2008) Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep. Nat Neurosci 11:200–208PubMedCrossRefGoogle Scholar
  81. 81.
    Vyazovskiy VV, Olcese U, Lazimy YM, Faraguna U, Esser SK, Williams JC, Cirelli C, Tononi G (2009) Cortical firing and sleep homeostasis. Neuron 63:865–878PubMedCrossRefGoogle Scholar
  82. 82.
    Walker JW, Jijon HB, Madsen KL (2006) AMP-activated protein kinase is a positive regulator of poly(ADP-ribose) polymerase. Biochem Biophys Res Commun 342:336–341PubMedCrossRefGoogle Scholar
  83. 83.
    Wang N, Yang G, Jia Z, Zhang H, Aoyagi T, Soodvilai S, Symons JD, Schnermann JB, Gonzalez FJ, Litwin SE, Yang T (2008) Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal1. Cell Metab 8:482–491PubMedCrossRefGoogle Scholar
  84. 84.
    Wigren HK, Rytkonen KM, Porkka-Heiskanen T (2009) Basal forebrain lactate release and promotion of cortical arousal during prolonged waking is attenuated in aging. J Neurosci 29:11698–11707PubMedCrossRefGoogle Scholar
  85. 85.
    Wisor JP, Clegern WC (2011) Quantification of short-term slow wave sleep homeostasis and its disruption by minocycline in the laboratory mouse. Neurosci Lett 490:165–169PubMedCrossRefGoogle Scholar
  86. 86.
    Wisor JP, Kilduff TS (2005) Molecular genetic advances in sleep research and their relevance to sleep medicine. Sleep 28:357–367PubMedGoogle Scholar
  87. 87.
    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
  88. 88.
    Wisor JP, Pasumarthi RK, Gerashchenko D, Thompson CL, Pathak S, Sancar A, Franken P, Lein ES, Kilduff TS (2008) Sleep deprivation effects on circadian clock gene expression in the cerebral cortex parallel electroencephalographic differences among mouse strains. J Neurosci 28:7193–7201PubMedCrossRefGoogle Scholar
  89. 89.
    Wisor JP, Schmidt MA, Clegern WC (2011) Evidence for neuroinflammatory and microglial changes in the cerebral response to sleep loss. Sleep 34:261–272PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.WWAMI Medical Education Program and Department Of Veterinary Comparative Anatomy, Pharmacology and PhysiologyWashington State UniversitySpokaneUSA

Personalised recommendations