Adenosine pp 253-272 | Cite as

The Bioenergetic Network of Adenosine in Hibernation, Sleep, and Thermoregulation

  • Kelly L. Drew
  • Tulasi R. Jinka


Adenosine is a homeostatic bioenergetic network regulator that plays a fundamental role in energy homeostasis through biochemical, bioenergetic, and receptor dependent processes. Hibernation, torpor, and sleep are integral to energy homeostasis. Here we review evidence that adenosine receptor dependent signaling as well as biochemical and bioenergetic influences of adenosine are essential to all three of these processes placing adenosine at the core of mammalian energy homeostasis. Central A1 adenosine receptor (A1R) dependent signaling is necessary for onset of hibernation and fasting-induced torpor in ground squirrels, hamsters, and mice. Activation of A1R within the central nervous system is sufficient to induce hibernation. A seasonally mediated change in sensitivity to central A1R stimulation is necessary for A1R agonist-induced hibernation in ground squirrels and may underlie the distinction between sleep and hibernation. One function of sleep is to restore brain energy homeostasis, while the primary function of hibernation and torpor is to restore or protect somatic energy homeostasis. Where in the brain A1R agonists act to induce torpor and how central A1R dependent signaling reduces metabolic rate to 1–2 % of resting metabolic rate in hibernating animals is a topic for further research. Understanding mechanisms of energy homeostasis may have implications for treatment of stroke, cardiac arrest, and other conditions where delivery of blood fails to meet demand.


Purinergic signaling AMPK ATP Torpor Ground squirrel 



This work was supported by US Army Research Office Grant W911NF-05-1-0280, US Army Medical Research and Materiel Command Grant 05178001, and National Institute of Neurological Disorders and Stroke Grants NS041069-06 and R15NS070779.


  1. Andrews MT (2004) Genes controlling the metabolic switch in hibernating mammals. Biochem Soc Trans 32:1021–1024CrossRefPubMedGoogle Scholar
  2. Andrews MT, Russeth KP, Drewes LR, Henry PG (2009) Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor. Am J Physiol Regul Integr Comp Physiol 296:R383–R393CrossRefPubMedGoogle Scholar
  3. Arrigoni E, Chamberlin NL, Saper CB, McCarley RW (2006) Adenosine inhibits basal forebrain cholinergic and noncholinergic neurons in vitro. Neuroscience 140:403–413CrossRefPubMedGoogle Scholar
  4. Asakura H (2004) Fetal and neonatal thermoregulation. J Nippon Med Sch 71:360–370CrossRefPubMedGoogle Scholar
  5. Atkins PW, De Paula J (2006) Atkins’ physical chemistry, 8th edn. W.H. Freeman, New YorkGoogle Scholar
  6. Barnes BM (1989) Freeze avoidance in a mammal: body temperatures below 0 degree C in an Arctic hibernator. Science 244:1593–1595CrossRefPubMedGoogle Scholar
  7. Barros RC, Branco LG (2000) Role of central adenosine in the respiratory and thermoregulatory responses to hypoxia. Neuroreport 11:193–197CrossRefPubMedGoogle Scholar
  8. Barros RC, Branco LG, Carnio EC (2006) Respiratory and body temperature modulation by adenosine A1 receptors in the anteroventral preoptic region during normoxia and hypoxia. Respir Physiol Neurobiol 153:115–125CrossRefPubMedGoogle Scholar
  9. Bauwens JD, Schmuck EG, Lindholm CR, Ertel RL, Mulligan JD, Hovis I, Viollet B, Saupe KW (2011) Cold tolerance, cold-induced hyperphagia and non-shivering thermogenesis are normal in {alpha}1 AMPK-/- mice. Am J Physiol Regul Integr Comp Physiol 301(2):R473–R483CrossRefPubMedGoogle Scholar
  10. Beccuti G, Pannain S (2011) Sleep and obesity. Curr Opin Clin Nutr Metab Care 14:402–412CrossRefPubMedGoogle Scholar
  11. Benington JH, Heller HC (1995) Restoration of brain energy metabolism as the function of sleep. Prog Neurobiol 45:347–360CrossRefPubMedGoogle Scholar
  12. Benington JH, Kodali SK, Heller HC (1995) Stimulation of A1 adenosine receptors mimics the electroencephalographic effects of sleep deprivation. Brain Res 692:79–85CrossRefPubMedGoogle Scholar
  13. Berger RJ, Phillips NH (1995) Energy conservation and sleep. Behav Brain Res 69:65–73CrossRefPubMedGoogle Scholar
  14. Blackstone E, Morrison M, Roth MB (2005) H2S induces a suspended animation-like state in mice. Science 308:518CrossRefPubMedGoogle Scholar
  15. Boison D, Masino SA, Geiger JD (2011) Homeostatic bioenergetic network regulation: a novel concept to avoid pharmacoresistance in epilepsy. Expert Opin Drug Discov 6:1–12CrossRefGoogle Scholar
  16. Bouma HR, Carey HV, Kroese FG (2010) Hibernation: the immune system at rest? J Leukoc Biol 88:619–624CrossRefPubMedGoogle Scholar
  17. Bouma HR, Kroese FG, Kok JW, Talaei F, Boerema AS, Herwig A, Draghiciu O, van Buiten A, Epema AH, van Dam A et al (2011) Low body temperature governs the decline of circulating lymphocytes during hibernation through sphingosine-1-phosphate. Proc Natl Acad Sci USA 108:2052–2057CrossRefPubMedGoogle Scholar
  18. Bratincsak A, McMullen D, Miyake S, Toth ZE, Hallenbeck JM, Palkovits M (2007) Spatial and temporal activation of brain regions in hibernation: c-fos expression during the hibernation bout in thirteen-lined ground squirrel. J Comp Neurol 505:443–458CrossRefPubMedGoogle Scholar
  19. Braulke LJ, Heldmaier G (2010) Torpor and ultradian rhythms require an intact signalling of the sympathetic nervous system. Cryobiology 60:198–203CrossRefPubMedGoogle Scholar
  20. Buck CL, Barnes BM (2000) Effects of ambient temperature on metabolic rate, respiratory quotient, and torpor in an arctic hibernator. Am J Physiol Regul Integr Comp Physiol 279:R255–R262PubMedGoogle Scholar
  21. Bushey D, Tononi G, Cirelli C (2011) Sleep and synaptic homeostasis: structural evidence in Drosophila. Science 332:1576–1581CrossRefPubMedGoogle Scholar
  22. Cano G, Passerin AM, Schiltz JC, Card JP, Morrison SF, Sved AF (2003) Anatomical substrates for the central control of sympathetic outflow to interscapular adipose tissue during cold exposure. J Comp Neurol 460:303–326CrossRefPubMedGoogle Scholar
  23. Carey HV, Andrews MT, Martin SL (2003) Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature. Physiol Rev 83:1153–1181PubMedGoogle Scholar
  24. Chikahisa S, Fujiki N, Kitaoka K, Shimizu N, Sei H (2009) Central AMPK contributes to sleep homeostasis in mice. Neuropharmacology 57:369–374CrossRefPubMedGoogle Scholar
  25. Contestabile A (2009) Benefits of caloric restriction on brain aging and related pathological States: understanding mechanisms to devise novel therapies. Curr Med Chem 16:350–361CrossRefPubMedGoogle Scholar
  26. Dausmann KH, Glos J, Ganzhorn JU, Heldmaier G (2004) Physiology: hibernation in a tropical primate. Nature 429:825–826CrossRefPubMedGoogle Scholar
  27. Drew KL, Buck CL, Barnes BM, Christian SL, Rasley BT, Harris MB (2007) Central nervous system regulation of mammalian hibernation: implications for metabolic suppression and ischemia tolerance. J Neurochem 102:1713–1726CrossRefPubMedGoogle Scholar
  28. Drew KL, Rice ME, Kuhn TB, Smith MA (2001) Neuroprotective adaptations in hibernation: therapeutic implications for ischemia-reperfusion, traumatic brain injury and neurodegenerative diseases. Free Radic Biol Med 31:563–573CrossRefPubMedGoogle Scholar
  29. Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24:31–55CrossRefPubMedGoogle Scholar
  30. Dworak M, McCarley RW, Kim T, Kalinchuk AV, Basheer R (2010) Sleep and brain energy levels: ATP changes during sleep. J Neurosci 30:9007–9016CrossRefPubMedGoogle Scholar
  31. Epperson LE, Karimpour-Fard A, Hunter LE, Martin SL (2011) Metabolic cycles in a circannual hibernator. Physiol Genomics 43(13):799–807CrossRefPubMedGoogle Scholar
  32. Florant GL, Fenn AM, Healy JE, Wilkerson GK, Handa RJ (2010) To eat or not to eat: the effect of AICAR on food intake regulation in yellow-bellied marmots (Marmota flaviventris). J Exp Biol 213:2031–2037CrossRefPubMedGoogle Scholar
  33. Florant GL, Turner BM, Heller HC (1978) Temperature regulation during wakefulness, sleep, and hibernation in marmots. Am J Physiol 235:R82–R88PubMedGoogle Scholar
  34. Florian C, Vecsey CG, Halassa MM, Haydon PG, Abel T (2011) Astrocyte-derived adenosine and A1 receptor activity contribute to sleep loss-induced deficits in hippocampal synaptic plasticity and memory in mice. J Neurosci 31:6956–6962CrossRefPubMedGoogle Scholar
  35. Fredholm BB, Johansson S, Wang YQ (2011) Adenosine and the regulation of metabolism and body temperature. Adv Pharmacol 61:77–94CrossRefPubMedGoogle Scholar
  36. French AR (1985) Allometries of the durations of torpid and euthermic intervals during mammalian hibernation: a test of the theory of metabolic control of the timing of changes in body temperature. J Comp Physiol B 156:13–19CrossRefPubMedGoogle Scholar
  37. Frerichs KU, Smith CB, Brenner M, DeGracia DJ, Krause GS, Marrone L, Dever TE, Hallenbeck JM (1998) Suppression of protein synthesis in brain during hibernation involves inhibition of protein initiation and elongation. Proc Natl Acad Sci USA 95:14511–14516CrossRefPubMedGoogle Scholar
  38. Fukuda M, Williams KW, Gautron L, Elmquist JK (2011) Induction of leptin resistance by activation of cAMP-Epac signaling. Cell Metab 13:331–339CrossRefPubMedGoogle Scholar
  39. Gallopin T, Luppi PH, Cauli B, Urade Y, Rossier J, Hayaishi O, Lambolez B, Fort P (2005) The endogenous somnogen adenosine excites a subset of sleep-promoting neurons via A2A receptors in the ventrolateral preoptic nucleus. Neuroscience 134:1377–1390CrossRefPubMedGoogle Scholar
  40. Galster W, Morrison PR (1975) Gluconeogenesis in arctic ground squirrels between periods of hibernation. Am J Physiol 228:325–330PubMedGoogle Scholar
  41. Galster WA, Morrison P (1970) Cyclic changes in carbohydrate concentrations during hibernation in the arctic ground squirrel. Am J Physiol 218:1228–1232PubMedGoogle Scholar
  42. Garcia MM, Gueant-Rodriguez RM, Pooya S, Brachet P, Alberto JM, Jeannesson E, Maskali F, Gueguen N, Marie PY, Lacolley P et al (2011) Methyl donor deficiency induces cardiomyopathy through altered methylation/acetylation of PGC-1alpha by PRMT1 and SIRT1. J Pathol 225(3):324–335CrossRefPubMedGoogle Scholar
  43. Geiser F (1988) Reduction of metabolism during hibernation and daily torpor in mammals and birds: temperature effect or physiological inhibition? J Comp Physiol B 158:25–37CrossRefPubMedGoogle Scholar
  44. Geiser F (2004) Metabolic rate and body temperature reduction during hibernation and daily torpor. Annu Rev Physiol 66:239–274CrossRefPubMedGoogle Scholar
  45. Geiser F, Song X, Körtner G (1996) The effect of He-O2 exposure on metabolic rate, thermoregulation and thermal conductance during normothermia and daily torpor. J Comp Physiol B 166:190–196CrossRefGoogle Scholar
  46. Gillooly JF, Brown JH, West GB, Savage VM, Charnov EL (2001) Effects of size and temperature on metabolic rate. Science 293:2248–2251CrossRefPubMedGoogle Scholar
  47. Glotzbach SF, Heller HC (1976) Central nervous regulation of body temperature during sleep. Science 194:537–539CrossRefPubMedGoogle Scholar
  48. Glotzbach SF, Heller HC (1984) Changes in the thermal characteristics of hypothalamic neurons during sleep and wakefulness. Brain Res 309:17–26CrossRefPubMedGoogle Scholar
  49. Hampton M, Nelson BT, Andrews MT (2010) Circulation and metabolic rates in a natural hibernator: an integrative physiological model. Am J Physiol Regul Integr Comp Physiol 299:R1478–R1488CrossRefPubMedGoogle Scholar
  50. Hardie DG (2008) AMPK: a key regulator of energy balance in the single cell and the whole organism. Int J Obes (Lond) 32 Suppl 4: S7–S12Google Scholar
  51. Heldmaier G, Ortmann S, Elvert R (2004) Natural hypometabolism during hibernation and daily torpor in mammals. Respir Physiol Neurobiol 141:317–329CrossRefPubMedGoogle Scholar
  52. Heller H (2005) Temperature, thermoregulation and sleep. In: Kryger M, Roth T, Dement W (eds) Principles and practice of sleep medicine. Elsevier Saunders, Philadelphia, pp 292–304CrossRefGoogle Scholar
  53. Heller HC, Colliver GW, Beard J (1977) Thermoregulation during entrance into hibernation. Pflugers Arch 369:55–59CrossRefPubMedGoogle Scholar
  54. Hochachka PW (1986) Defense strategies against hypoxia and hypothermia. Science 231:234–241CrossRefPubMedGoogle Scholar
  55. Hoffman RA, Robinson PF, Magalhaes H (eds) (1968) The golden hamster; its biology and use in medical research. The Iowa State University Press, Ames Iowa, USAGoogle Scholar
  56. Huang ZL, Qu WM, Eguchi N, Chen JF, Schwarzschild MA, Fredholm BB, Urade Y, Hayaishi O (2005) Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci 8:858–859PubMedGoogle Scholar
  57. Huang ZL, Urade Y, Hayaishi O (2007) Prostaglandins and adenosine in the regulation of sleep and wakefulness. Curr Opin Pharmacol 7:33–38CrossRefPubMedGoogle Scholar
  58. Jinka TJ, Toien O, Drew KL (2011) Season primes the brain in an arctic hibernator to facilitate entrance into torpor mediated by adenosine A1 receptors. J Neurosci 31(30):10752–10758CrossRefPubMedGoogle Scholar
  59. Jinka TR, Carlson ZA, Moore JT, Drew KL (2010) Altered thermoregulation via sensitization of A1 adenosine receptors in dietary restricted rats. Psychopharmacology (Berl) 209(3):217–224CrossRefGoogle Scholar
  60. Karpovich SA, Toien O, Buck CL, Barnes BM (2009) Energetics of arousal episodes in hibernating arctic ground squirrels. J Comp Physiol B 179:691–700CrossRefPubMedGoogle Scholar
  61. Katayose Y, Tasaki M, Ogata H, Nakata Y, Tokuyama K, Satoh M (2009) Metabolic rate and fuel utilization during sleep assessed by whole-body indirect calorimetry. Metabolism 58:920–926CrossRefPubMedGoogle Scholar
  62. Kilduff TS, Krilowicz B, Milsom WK, Trachsel L, Wang LC (1993) Sleep and mammalian hibernation: homologous adaptations and homologous processes? Sleep 16:372–386PubMedGoogle Scholar
  63. Kruman II (1992) Comparative analysis of cell replacement in hibernators. Comp Biochem Physiol A 101:11–18CrossRefPubMedGoogle Scholar
  64. Latini S, Pedata F (2001) Adenosine in the central nervous system: release mechanisms and extracellular concentrations. J Neurochem 79:463–484CrossRefPubMedGoogle Scholar
  65. Lee TF, Nurnberger F, Wang LCH (eds) (1993) Possible involvement of endogenous adenosine in hibernation. Westview, BoulderGoogle Scholar
  66. Lee TM, Zucker I (1991) Suprachiasmatic nucleus and photic entrainment of circannual rhythms in ground squirrels. J Biol Rhythms 6:315–330CrossRefPubMedGoogle Scholar
  67. Levesque DL, Tattersall GJ (2009) Seasonal changes in thermoregulatory responses to hypoxia in the Eastern chipmunk (Tamias striatus). J Exp Biol 212:1801–1810CrossRefPubMedGoogle Scholar
  68. Lim CT, Kola B, Korbonits M (2010) AMPK as a mediator of hormonal signalling. J Mol Endocrinol 44:87–97CrossRefPubMedGoogle Scholar
  69. Liu ZW, Gao XB (2007) Adenosine inhibits activity of hypocretin/orexin neurons by the A1 receptor in the lateral hypothalamus: a possible sleep-promoting effect. J Neurophysiol 97:837–848CrossRefPubMedGoogle Scholar
  70. Lust WD, Wheaton AB, Feussner G, Passonneau J (1989) Metabolism in the hamster brain during hibernation and arousal. Brain Res 489:12–20CrossRefPubMedGoogle Scholar
  71. Lyman C, O’Brien R (1960) Circulatory changes in the thirteen-lined ground squirrel during the hibernation cycle. In Mammalian Hibernation Bull Mus Comp Zool, 353–372Google Scholar
  72. Ma YL, Zhu X, Rivera PM, Toien O, Barnes BM, LaManna JC, Smith MA, Drew KL (2005) Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels. Am J Physiol Regul Integr Comp Physiol 289:R1297–R1306CrossRefPubMedGoogle Scholar
  73. Magarinos AM, McEwen BS, Saboureau M, Pevet P (2006) Rapid and reversible changes in intrahippocampal connectivity during the course of hibernation in European hamsters. Proc Natl Acad Sci USA 103:18775–18780CrossRefPubMedGoogle Scholar
  74. Muleme HM, Walpole AC, Staples JF (2006) Mitochondrial metabolism in hibernation: metabolic suppression, temperature effects, and substrate preferences. Physiol Biochem Zool 79:474–483CrossRefPubMedGoogle Scholar
  75. Mulligan JD, Gonzalez AA, Stewart AM, Carey HV, Saupe KW (2007) Upregulation of AMPK during cold exposure occurs via distinct mechanisms in brown and white adipose tissue of the mouse. J Physiol 580:677–684CrossRefPubMedGoogle Scholar
  76. Nakamura K (2011) Central circuitries for body temperature regulation and fever. Am J Physiol Regul Integr Comp Physiol 301:R1207–R1228CrossRefPubMedGoogle Scholar
  77. Oishi Y, Huang ZL, Fredholm BB, Urade Y, Hayaishi O (2008) Adenosine in the tuberomammillary nucleus inhibits the histaminergic system via A1 receptors and promotes non-rapid eye movement sleep. Proc Natl Acad Sci USA 105:19992–19997CrossRefPubMedGoogle Scholar
  78. Osborne PG, Sato J, Shuke N, Hashimoto M (2005) Sympathetic alpha-adrenergic regulation of blood flow and volume in hamsters arousing from hibernation. Am J Physiol Regul Integr Comp Physiol 289:R554–R562CrossRefPubMedGoogle Scholar
  79. Pastukhov YF (1997) REM sleep as a criterion of temperature comfort and temperature homeostasis “well-being” in euthermic and hibernating mammals. Ann N Y Acad Sci 813:71–72CrossRefPubMedGoogle Scholar
  80. Pek M, Lutz PL (1997) Role for adenosine in channel arrest in the anoxic turtle brain. J Exp Biol 200:1913–1917PubMedGoogle Scholar
  81. Pengelley ET, Asmundson SJ, Barnes B, Aloia RC (1976) Relationship of light intensity and photoperiod to circannual rhythmicity in the hibernating ground squirrel, Citellus lateralis. Comp Biochem Physiol A 53:273–277CrossRefPubMedGoogle Scholar
  82. Popov VI, Bocharova LS (1992) Hibernation-induced structural changes in synaptic contacts between mossy fibres and hippocampal pyramidal neurons. Neuroscience 48:53–62CrossRefPubMedGoogle Scholar
  83. Popov VI, Kraev IV, Ignat’ev DA, Stewart MG (2011) Suspension of mitotic activity in dentate gyrus of the hibernating ground squirrel. Neural Plast 2011:867525CrossRefPubMedGoogle Scholar
  84. Porkka-Heiskanen T, Kalinchuk AV (2011) Adenosine, energy metabolism and sleep homeostasis. Sleep Med Rev 15:123–135CrossRefPubMedGoogle Scholar
  85. Porkka-Heiskanen T, Strecker RE, McCarley RW (2000) Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: an in vivo microdialysis study. Neuroscience 99:507–517CrossRefPubMedGoogle Scholar
  86. Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjorkum AA, Greene RW, McCarley RW (1997) Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science 276:1265–1268CrossRefPubMedGoogle Scholar
  87. Pulawa LK, Florant GL (2000) The effects of caloric restriction on the body composition and hibernation of the golden-mantled ground squirrel (Spermophilus lateralis). Physiol Biochem Zool 73:538–546CrossRefPubMedGoogle Scholar
  88. Rivkees SA, Price SL, Zhou FC (1995) Immunohistochemical detection of A1 adenosine receptors in rat brain with emphasis on localization in the hippocampal formation, cerebral cortex, cerebellum, and basal ganglia. Brain Res 677:193–203CrossRefPubMedGoogle Scholar
  89. Russell RL, O’Neill PH, Epperson LE, Martin SL (2010) Extensive use of torpor in 13-lined ground squirrels in the fall prior to cold exposure. J Comp Physiol B 180:1165–1172CrossRefPubMedGoogle Scholar
  90. Satoh S, Matsumura H, Kanbayashi T, Yoshida Y, Urakami T, Nakajima T, Kimura N, Nishino S, Yoneda H (2006) Expression pattern of FOS in orexin neurons during sleep induced by an adenosine A2A receptor agonist. Behav Brain Res 170:277–286CrossRefPubMedGoogle Scholar
  91. Scharf MT, Naidoo N, Zimmerman JE, Pack AI (2008) The energy hypothesis of sleep revisited. Prog Neurobiol 86:264–280CrossRefPubMedGoogle Scholar
  92. Schmidt-Nielsen K (1997) Animal physiology: adaptation and environment, 5th edn. Cambridge University Press, CambridgeGoogle Scholar
  93. Serkova NJ, Rose JC, Epperson LE, Carey HV, Martin SL (2007) Quantitative analysis of liver metabolites in three stages of the circannual hibernation cycle in 13-lined ground squirrels by NMR. Physiol Genomics 31:15–24CrossRefPubMedGoogle Scholar
  94. Sheriff MJ, Kenagy GJ, Richter M, Lee T, Toien O, Kohl F, Buck CL, Barnes BM (2010) Phenological variation in annual timing of hibernation and breeding in nearby populations of Arctic ground squirrels. Proc Biol Sci 278(1716):2369–2375CrossRefPubMedGoogle Scholar
  95. Sherin JE, Shiromani PJ, McCarley RW, Saper CB (1996) Activation of ventrolateral preoptic neurons during sleep. Science 271:216–219CrossRefPubMedGoogle Scholar
  96. Shiomi H, Tamura Y (2000) Pharmacological aspects of mammalian hibernation: central thermoregulation factors in hibernation cycle. Nippon Yakurigaku Zasshi (Folia Pharmacol Jpn) 116:304–312CrossRefGoogle Scholar
  97. Snyder GK, Nestler JR (1990) Relationships between body temperature, thermal conductance, Q10 and energy metabolism during daily torpor and hibernation in rodents. J Comp Physiol B 159:667–675CrossRefPubMedGoogle Scholar
  98. St-Onge MP, Roberts AL, Chen J, Kelleman M, O’Keeffe M, Roychoudhury A, Jones PJ (2011) Short sleep duration increases energy intakes but does not change energy expenditure in normal-weight individuals. Am J Clin Nutr 94:410–416CrossRefPubMedGoogle Scholar
  99. Staples JF, Brown JC (2008) Mitochondrial metabolism in hibernation and daily torpor: a review. J Comp Physiol B 178:811–827CrossRefPubMedGoogle Scholar
  100. Steiner AA, Branco LG (2002) Hypoxia-induced anapyrexia: implications and putative mediators. Annu Rev Physiol 64:263–288CrossRefPubMedGoogle Scholar
  101. 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 115:183–204CrossRefPubMedGoogle Scholar
  102. Strijkstra AM, Daan S (1997) Sleep during arousal episodes as a function of prior torpor duration in hibernating European ground squirrels. J Sleep Res 6:36–43CrossRefPubMedGoogle Scholar
  103. Swoap S, Lliff B (2011) AMP vs. adenosine as a mediator of fasting-induced torpor. Paper presented at metabolic responses to extreme conditions, keystone symposia on molecular and cellular biology, Big Sky, MontanaGoogle Scholar
  104. Swoap SJ, Gutilla MJ, Liles LC, Smith RO, Weinshenker D (2006) The full expression of fasting-induced torpor requires beta 3-adrenergic receptor signaling. J Neurosci 26:241–245CrossRefPubMedGoogle Scholar
  105. Swoap SJ, Rathvon M, Gutilla M (2007) AMP does not induce torpor. Am J Physiol Regul Integr Comp Physiol 293:R468–R473CrossRefPubMedGoogle Scholar
  106. Swoap SJ, Weinshenker D (2008) Norepinephrine controls both torpor initiation and emergence via distinct mechanisms in the mouse. PLoS One 3:e4038CrossRefPubMedGoogle Scholar
  107. Tamura Y, Shintani M, Nakamura A, Monden M, Shiomi H (2005) Phase-specific central regulatory systems of hibernation in Syrian hamsters. Brain Res 1045:88–96CrossRefPubMedGoogle Scholar
  108. Tattersall GJ, Milsom WK (2003) Transient peripheral warming accompanies the hypoxic metabolic response in the golden-mantled ground squirrel. J Exp Biol 206:33–42CrossRefPubMedGoogle Scholar
  109. Ticho SR, Radulovacki M (1991) Role of adenosine in sleep and temperature regulation in the preoptic area of rats. Pharmacol Biochem Behav 40:33–40CrossRefPubMedGoogle Scholar
  110. Toien O, Blake J, Edgar DM, Grahn DA, Heller HC, Barnes BM (2011) Hibernation in black bears: independence of metabolic suppression from body temperature. Science 331:906–909CrossRefPubMedGoogle Scholar
  111. Toien O, Drew KL, Chao ML, Rice ME (2001) Ascorbate dynamics and oxygen consumption during arousal from hibernation in Arctic ground squirrels. Am J Physiol Regul Integr Comp Physiol 281:R572–R583PubMedGoogle Scholar
  112. Twente JW, Twente JA (1968) Progressive irritability of hibernating Citellus lateralis. Comp Biochem Physiol 25:467–474CrossRefPubMedGoogle Scholar
  113. Ungvari Z, Parrado-Fernandez C, Csiszar A, de Cabo R (2008) Mechanisms underlying caloric restriction and lifespan regulation: implications for vascular aging. Circ Res 102:519–528CrossRefPubMedGoogle Scholar
  114. von der Ohe CG, Garner CC, Darian-Smith C, Heller HC (2007) Synaptic protein dynamics in hibernation. J Neurosci 27:84–92CrossRefPubMedGoogle Scholar
  115. Walker JM, Glotzbach SF, Berger RJ, Heller HC (1977) Sleep and hibernation in ground squirrels (Citellus spp): electrophysiological observations. Am J Physiol 233:R213–R221PubMedGoogle Scholar
  116. Walker JM, Haskell EH, Berger RJ, Heller CH (1980) Hibernation and circannual rhythms of sleep. Physiol Zool 53:8–11Google Scholar
  117. Walther T, Novo M, Rossger K, Letisse F, Loret MO, Portais JC, Francois JM (2010) Control of ATP homeostasis during the respiro-fermentative transition in yeast. Mol Syst Biol 6:344CrossRefPubMedGoogle Scholar
  118. Wilson CN (2009) Adenosine receptors in health and disease. Springer, New YorkCrossRefGoogle Scholar
  119. Zhang J, Kaasik K, Blackburn MR, Lee CC (2006) Constant darkness is a circadian metabolic signal in mammals. Nature 439:340–343CrossRefPubMedGoogle Scholar
  120. Zhu PJ, Krnjevic K (1997) Adenosine release mediates cyanide-induced suppression of CA1 neuronal activity. J Neurosci 17:2355–2364PubMedGoogle Scholar
  121. Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M, Lass A, Neuberger G, Eisenhaber F, Hermetter A et al (2004) Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306:1383–1386CrossRefPubMedGoogle Scholar
  122. zur Nedden S, Hawley S, Pentland N, Hardie DG, Doney AS, Frenguelli BG (2011) Intracellular ATP influences synaptic plasticity in area CA1 of rat hippocampus via metabolism to adenosine and activity-dependent activation of adenosine A1 receptors. J Neurosci 31:6221–6234CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Alaska Basic Neuroscience Program, Department of Chemistry and Biochemistry, Institute of Arctic BiologyUniversity of Alaska FairbanksFairbanksUSA

Personalised recommendations