Ghrelin in mental health, sleep, memory

Molecular and Cellular Endocrinology

Volumn 340, Issue 1, 2011, Pages 88-96

  Steiger, Axel ^a   Dresler, Martin ^a   Schüssler, Petra ^a   Kluge, Michael ^a,b  

^a MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

^b UNIVERSITY OF LEIPZIG   (Germany)

Author keywords

Depression; Ghrelin; Memory; Mental health; Sleep

Indexed keywords

GHRELIN; GROWTH HORMONE; GROWTH HORMONE RELEASING FACTOR; HYDROCORTISONE; PROLACTIN;

BRAIN REGION; COGNITION; DEPRESSION; DNA POLYMORPHISM; EPILEPSY; GENOTYPE; HORMONE BLOOD LEVEL; HORMONE RELEASE; HORMONE RESPONSE; HUMAN; HYDROCORTISONE BLOOD LEVEL; LONG TERM MEMORY; MEMORY; MEMORY CONSOLIDATION; MENTAL DISEASE; MENTAL HEALTH; NEUROLOGIC DISEASE; NONHUMAN; NONREM SLEEP; PRIORITY JOURNAL; REM SLEEP; REVIEW; SLEEP; SLEEP STAGE; SOCIAL AVOIDANCE BEHAVIOR; SPATIAL MEMORY; WAKEFULNESS;

ANIMALS; DEPRESSION; GHRELIN; HUMANS; MEMORY; MENTAL HEALTH; NERVOUS SYSTEM DISEASES; SEX CHARACTERISTICS; SLEEP;

EID: 79958167390     PISSN: 03037207     EISSN: 18728057     Source Type: Journal    
DOI: 10.1016/j.mce.2011.02.013     Document Type: Review

References (86)

1. Allison K.C., Ahima R.S., O'Reardon J.P., Dinges D.F., Sharma V., Cummings D.E., Heo M., Martino N.S., Stunkard A.J. Neuroendocrine profiles associated with energy intake, sleep, and stress in the night eating syndrome. J. Clin. Endocrinol. Metab. 2005, 90:6214-6217.
2. American Academy of Sleep Medicine, Iber C., Anoli-Israel S., Chesson A., Quan S.F. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications 2007, American Academy of Sleep Medicine, Westchester, IL.
3. Antonijevic I.A., Murck H., Frieboes R.M., Barthelmes J., Steiger A. Sexually dimorphic effects of GHRH on sleep-endocrine activity in patients with depression and normal controls - part I: the sleep EEG. Sleep Res. Online 2000, 3:5-13.
4. Antonijevic I.A., Murck H., Frieboes R.M., Steiger A. Sexually dimorphic effects of GHRH on sleep-endocrine activity in patients with depression and normal controls - part II: hormone secretion. Sleep Res. Online 2000, 3:15-21.
5. Asakawa A., Inui A., Kaga T., Yuzuriha H., Nagata T., Fujimiya M., Katsuura G., Makino S., Fujino M.A., Kasuga M. A role of ghrelin in neuroendocrine and behavioral responses to stress in mice. Neuroendocrinology 2001, 74:143-147.
6. Albouy G., Sterpenich V., Balteau E., Vandewalle G., Desseilles M., Dang-Vu T., Darsaud A., Ruby P., Luppi P.H., Degueldre C., Peigneux P., Luxen A., Maquet P Both the hippocampus and striatum are involved in consolidation of motor sequence memory. Neuron 2008, 58:261-272.
7. Atcha Z., Chen W.S., Ong A.B., Wong F.K., Neo A., Browne E.R., Witherington J., Pemberton D.J. Cognitive enhancing effects of ghrelin receptor agonists. Psychopharmacology 2009, 206:415-427.
8. Berilgen M.S., Mungen B., Ustundag B., Demir C. Serum ghrelin levels are enhanced in patients with epilepsy. Seizure 2006, 15:106-111.
9. Bodosi B., Gardi J., Hajdu I., Szentirmai E., Obál F., Krueger J.M. 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. 2004, 287:R1071-R1079.
10. Borbély A.A. A two process model of sleep regulation. Hum. Neurobiol. 1982, 1:195-204.
11. Carlini V.P., Monzon M.E., Varas M.M., Cragnolini A.B., Schioth H.B., Scimonelli T.N., de Barioglio S.R. Ghrelin increases anxiety-like behavior and memory retention in rats. Biochem. Biophys. Res. Commun. 2002, 299:739-743.
12. Carlini V.P., Varas M.M., Cragnolini A.B., Schioth H.B., Scimonelli T.N., de Barioglio S.R. Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in regulating feeding, memory, and anxiety-like behavioral responses to ghrelin. Biochem. Biophys. Res. Commun. 2004, 313:635-641.
13. Carlini V.P., Martini A.C., Schioth H.B., Ruiz R.D., Fiol de Cuneo M., de Barioglio S.R. Decreased memory for novel object recognition in chronically food-restricted mice is reversed by acute ghrelin administration. Neuroscience 2008, 153:929-934.
14. Carlini V., Ghersi M., Schiöth H.B., de Barioglio S.R. Ghrelin and memory: differential effects on acquisition and retrieval. Peptides 2010, 31:1190-1193.
15. Carlini V., Perez M.F., Salde E., Schiöth H.B., Ramirez O.A., de Barioglio S.R. Ghrelin induced memory facilitation implicates nitric oxide synthase activation and decrease in the threshold to promote LTP in hippocampal dentate gyrus. Physiol. Behav. 2010, 101:117-123.
16. Carvajal P., Carlini V.P., Schiöth H.B., de Barioglio S., Salvatierra NA Central ghrelin increases anxiety in the Open Field test and impairs retention memory in a passive avoidance task in neonatal chicks. Neurobiol. Learn. Mem. 2009, 91:402-407.
17. Copinschi G., Leproult R., Van Onderbergen A., Caufriez A., Cole K.Y., Schilling L.M., Mendel C.M., De Lepeleire I., Bolognese J.A., Van Cauter E. Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. Neuroendocrinology 1997, 66:278-286.
18. Cummings D.E., Purnell J.Q., Frayo R.S., Schmidova K., Wisse B.E., Weigle D.S. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001, 50:1714-1719.
19. Davis, J.F., Choi, D.L., Clegg, D.J., Benoit, S.C. Signaling through the ghrelin receptor modulates hippocampal function and meal anticipation in mice. Physiol. Behav., in press.
20. Diano S., Farr S.A., Benoit S.C., McNay E.C., da Silva I., Horvath B., Gaskin F.S., Nonaka N., Jaeger L.B., Banks W.A., Morley J.E., Pinto S., Sherwin R.S., Xu L., Yamada K.A., Sleeman M.W., Tschop M.H., Horvath T.L. Ghrelin controls hippocampal spine synapse density and memory performance. Nat. Neurosci. 2006, 9:381-388.
21. Dresler M., Kluge M., Genzel L., Schüssler P., Steiger A. Nocturnal administration of ghrelin does not promote memory consolidation. Pharmacopsychiatry 2010, 43:277-278.
22. Dzaja A., Dalal M.A., Himmerich H., Uhr M., Pollmächer T., Schuld A. Sleep enhances nocturnal plasma ghrelin levels in healthy subjects. Am. J. Physiol. Endocrinol. Metab. 2004, 286:E963-E967.
23. Ehlers C.L., Kupfer D.J. Slow-wave sleep: do young adult men and women age differently?. J. Sleep Res. 1997, 6:211-215.
24. Ehlers C.L., Reed T.K., Henriksen S.J. Effects of corticotropin-releasing factor and growth hormone- releasing factor on sleep and activity in rats. Neuroendocrinology 1986, 42:467-474.
25. Emül H.M., Serteser M., Kurt E., Ozbulut O., Guler O., Gecici O. Ghrelin and leptin levels in patients with obsessive-compulsive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 2007, 31:1270-1274.
26. Fernandez-Fernandez R., Tena-Sempere M., Navarro V.M., Barreiro M.L., Castellano J.M., Aguilar E., Pinilla L. Effects of ghrelin upon gonadotropin-releasing hormone and gonadotropin secretion in adult female rats: in vivo and in vitro studies. Neuroendocrinology 2005, 82:245-255.
27. Frieboes R.M., Murck H., Maier P., Schier T., Holsboer F., Steiger A. Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH and cortisol release in normal man. Neuroendocrinology 1995, 61:584-589.
28. Frieboes R.M., Murck H., Antonijevic I.A., Steiger A. Effects of growth hormone-releasing peptide-6 on the nocturnal secretion of GH, ACTH and cortisol and on the sleep EEG in man: role of routes of administration. J. Neuroendocrinol. 1999, 11:473-478.
29. Frieboes R.M., Antonijevic I.A., Held K., Murck H., Pollmächer T., Uhr M., Steiger A. Hexarelin decreases slow-wave sleep and stimulates the sleep-related secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers. Psychoneuroendocrinology 2004, 29:851-860.
30. Furuta M., Funabashi T., Kimura F. Intracerebroventricular administration of ghrelin rapidly suppresses pulsatile luteinizing hormone secretion in ovariectomized rats. Biochem. Biophys. Res. Commun. 2001, 288:780-785.
31. Guldner J., Schier T., Friess E., Colla M., Holsboer F., Steiger A. Reduced efficacy of growth hormone-releasing hormone in modulating sleep endocrine activity in the elderly. Neurobiol. Aging 1997, 18:491-495.
32. Holsboer F., von Bardeleben U., Steiger A. Effects of intravenous corticotropin-releasing hormone upon sleep-related growth hormone surge and sleep EEG in man. Neuroendocrinology 1988, 48:32-38.
33. Kanehisa M., Akiyoshi J., Kitaichi T., Matsushita H., Tanaka E., Kodama K., Hanada H., Isogawa K. Administration of antisense DNA for ghrelin causes an antidepressant and anxiolytic response in rats. Prog. Neuropsychopharmacol. Biol. Psychiatry 2006, 30:1403-1407.
34. Kerkhofs M., Van Cauter E., Van Onderbergen A., Caufriez A., Thorner M.O., Copinschi G. Sleep-promoting effects of growth hormone-releasing hormone in normal men. Am. J. Physiol. Endocrinol. Metab. 1993, 264:E594-E598.
35. Kimura M., Müller-Preuss P., Lu A., Wiesner E., Flachskamm C., Wurst W., Holsboer F., Deussing J.M. Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep. Mol. Psychiatr. 2010, 15:154-165.
36. Kluge M., Schüssler P., Uhr M., Yassouridis A., Steiger A. Ghrelin suppresses secretion of luteinizing hormone in humans. J. Clin. Endocrinol. Metab. 2007, 92:3202-3205.
37. Kluge M., Schüssler P., Zuber V., Kleyer S., Yassouridis A., Dresler M., Uhr M., Steiger A. Ghrelin enhances the nocturnal secretion of cortisol and growth hormone in young females without influencing sleep. Psychoneuroendocrinology 2007, 32:1079-1085.
38. Kluge M., Schüssler P., Zuber V., Yassouridis A., Steiger A. Ghrelin administered in the early morning increases secretion of cortisol and growth hormone without affecting sleep. Psychoneuroendocrinology 2007, 32:287-292.
39. Kluge M., Schüssler P., Bleninger P., Kleyer S., Uhr M., Weikel J.C., Yassouridis A., Zuber V., Steiger A. Ghrelin alone or co-administered with GHRH or CRH increases non-REM sleep and decreases REM sleep in young males. Psychoneuroendocrinology 2008, 33:497-506.
40. Kluge M., Schüssler P., Schmid D., Uhr M., Kleyer S., Yassouridis A., Steiger A. Ghrelin plasma levels are not altered in major depression. Neuropsychobiology 2009, 59:199-204.
41. Kluge M., Uhr M., Bleninger P., Yassouridis A., Steiger A. Ghrelin suppresses secretion of FSH in males. Clin. Endocrinol. 2009, 70:920-923.
42. Kluge M., Gazea M., Schüssler P., Genzel L., Dresler M., Kleyer S., Uhr M., Yassouridis A., Steiger A. Ghrelin increases slow wave sleep and stage 2 sleep and decreases stage 1 sleep and REM sleep in elderly men but does not affect sleep in elderly women. Psychoneuroendocrinology 2010, 35:297-304.
43. Kluge M., Riedl S., Uhr M., Schmidt D., Zhang X., Yassouridis A., Steiger A. Ghrelin affects the hypothalamus-pituitary-thyroid axis in humans by increasing free thyroxine and decreasing TSH in plasma. Eur. J. Endocrinol. 2010, 162:1059-1065.
44. Kluge M., Schüssler P., Dresler M., Schmidt D., Yassouridis A., Uhr M., Steiger A. Effects of ghrelin on psychopathology, sleep and secretion of cortisol and growth hormone in patients with major depression. J. Psychiatr. Res. 2011, 45:421-426.
45. Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H., Kangawa K. Ghrelin is a growth hormone-releasing acylated peptide from stomach. Nature 1999, 402:656-660.
46. Krueger J.M., Majde J.A., Rector D.M. Cytokines in immune function and sleep regulation. Handbook of Clinical Neurology 2011, 229-240. Elsevier B.V., Amsterdam. P. Montagna, S. Chokroverty (Eds.).
47. Luppi P.H., Fort P. Neurochemistry of sleep: an overview of animal experimental work. Handbook of Clinical Neurology 2011, 173-190. Elsevier B.V., Amsterdam. P. Montagna, S. Chokroverty (Eds.).
48. Lutter M., Sakata I., Osborne-Lawrence S., Rovinsky S.A., Anderson J.G., Jung S., Birnbaum S., Yanagisawa M., Elmquist J.K., Nestler E.J., Zigman J.M. The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nat. Neurosci. 2008, 11:752-753.
49. Malik S., McGlone F., Bedrossian D., Dagher A Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metab. 2008, 7:400-409.
50. Marshall L., Mölle M., Böschen G., Steiger A., Fehm H.L., Born J. Greater efficacy of episodic than continuous growth hormone releasing hormone (GHRH) administration in promoting slow wave sleep (SWS). J. Clin. Endocrinol. Metab. 1996, 81:1009-1013.
51. Moon M., Choi J.G., Nam D.W., Hong H.S., Choi Y.J., Oh M.S., Mook-Jung I. Ghrelin ameliorates cognitive dysfunction and neurodegeneration in intrahippocampal amyloid-β1-42 oligomer-injected mice. J. Alzheimers Dis. 2010, 23:1-13.
52. Moreno-Reyes R., Kerkhofs M., L'Hermite-Balériaux M., Thorner M.O., Van Cauter E., Copinschi G. Evidence against a role for the growth hormone-releasing peptide axis in human slow-wave sleep regulation. Am. J. Physiol. Endocrinol. Metab. 1998, 274:E779-E784.
53. Motivala S.J., Tomiyama A.J., Ziegler M., Khandrika S., Irwin M.R. Nocturnal levels of ghrelin and leptin and sleep in chronic insomnia. Psychoneuroendocrinology 2009, 34:540-545.
54. Murashita M., Kusumi I., Inoue T., Takahashi Y., Hosoda H., Kangawa K., Koyama T. Olanzapine increases plasma ghrelin level in patients with schizophrenia. Psychoneuroendocrinology 2005, 30:106-110.
55. Nakashima K., Akiyoshi J., Hatano K., Hanada H., Tanaka Y., Tsuru J., Matsushita H., Kodama K., Isogawa K. Ghrelin gene polymorphism is associated with depression, but not panic disorder. Psychiatr. Genet. 2008, 18:257.
56. Obál F., Sary G., Alföldi P., Rubicsek G. Vasoactive intestinal polypeptide promotes sleep without effects on brain temperature in rats at night. Neurosci. Lett. 1986, 64:236-240.
57. Obál F., Payne L., Opp M., Alföldi P., Kapás L., Krueger J.M. Growth hormone-releasing hormone antibodies suppress sleep and prevent enhancement of sleep after sleep deprivation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 1992, 263:R1078-R1085.
58. Obál F., Floyd R., Kapás L., Bodosi B., Krueger J.M. Effects of systemic GHRH on sleep in intact and in hypophysectomized rats. Am. J. Physiol. Endocrinol. Metab. 1996, 270:E230-E237.
59. Obál F., Alt J., Taishi P., Gardi J., Krueger J.M. Sleep in mice with non-functional growth hormone-releasing hormone receptors. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2003, 284:R131-R139.
60. Obál F., Krueger J.M. GHRH and sleep. Sleep Medicine Rev. 2004, 8:367-377.
61. Olszewski P.K., Schiöth H.B., Levine A.S. Ghrelin in the CNS: from hunger to a rewarding and memorable meal?. Brain Res. Rev. 2008, 58:160-170.
62. Otto B., Cuntz U., Fruehauf E., Wawarta R., Folwaczny C., Riepl R.L., Heiman M.L., Lehnert P., Fichter M., Tschöp M. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur. J. Endocrinol. 2001, 145:R5-R9.
63. Paik K.H., Jin D.K., Song S.Y., Lee J.E., Ko S.H., Song S.M., Kim J.S., Oh Y.J., Kim S.W., Lee S.H., Kim S.H., Kwon E.K., Choe Y.H. Correlation between fasting plasma ghrelin levels and age, body mass index (BMI), BMI percentiles, and 24-hour plasma ghrelin profiles in Prader-Willi syndrome. J. Clin. Endocrinol. Metab. 2004, 89:3885-3889.
64. Perras B., Marshall L., Köhler G., Born J., Fehm H.L. Sleep and endocrine changes after intranasal administration of growth hormone-releasing hormone in young and aged humans. Psychoneuroendocrinology 1999, 24:743-757.
65. Rechtschaffen A., Kales A. A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects 1968, US Department of Health, Education & Welfare, Neurological Information Network, Bethesda, MD.
66. Rosenhagen M.C., Uhr M., Schüssler P., Steiger A. Elevated plasma ghrelin levels in night-eating syndrome. Am. J. Psychiatry 2005, 162:813.
67. Schier T., Guldner J., Colla M., Holsboer F., Steiger A. Changes in sleep-endocrine activity after growth hormone-releasing hormone depend on time of administration. J. Neuroendocrinol. 1997, 9:201-205.
68. Schmid D.A., Held K., Ising M., Uhr M., Weikel J.C., Steiger A. Ghrelin stimulates appetite, imagination of food, GH, ACTH and cortisol, but does not affect leptin in normal controls. Neuropsychopharmacology 2005, 30:1187-1192.
69. Schmid D.A., Wichniak A., Uhr M., Ising M., Brunner H., Held K., Weikel J., Sonntag A., Steiger A. Changes of sleep architecture, spectral composition of sleep EEG, the nocturnal secretion of cortisol, ACTH, GH, prolactin, melatonin, ghrelin and leptin and the DEX-CRH test in depressed patients during treatment with mirtazapine. Neuropsychopharmacology 2006, 31:832-844.
70. Schüssler P., Uhr M., Ising M., Schmid D., Weikel J., Steiger A. Nocturnal ghrelin levels - relationship to sleep EEG, the levels of growth hormone, ACTH and cortisol - and gender differences. J. Sleep Res. 2005, 14:329-336.
71. Sosic-Jurjevic B., Stevanovic D., Milosevic V., Sekulic M., Starcevic V. Central ghrelin affects pituitary-thyroid axis: histomorphological and hormonal study in rats. Neuroendocrinology 2009, 89:327-336.
72. Spiegel K., Tasali E., Penev P., Van Cauter E. 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. 2004, 141:846-850.
73. Spitznagel M.B., Benitez A., Updegraff J., Potter V., Alexander T., Glickman E., Gunstadt J. Serum ghrelin is inversely associated with cognitive function in a sample of non-demented elderly. Psychiatry Clin. Neurosci. 2010, 64:608-611.
74. Steiger A., Guldner J., Hemmeter U., Rothe B., Wiedemann K., Holsboer F. Effects of growth hormone-releasing hormone and somatostatin on sleep EEG and nocturnal hormone secretion in male controls. Neuroendocrinology 1992, 56:566-573.
75. Steiger A. Neurochemical regulation of sleep. J. Psychiatr. Res. 2007, 41:537-552.
76. Szentirmai E., Hajdu I., Obál F., Krueger J.M. Ghrelin-induced sleep responses in ad libitum fed and food-restricted rats. Brain Res. 2006, 1088:131-140.
77. Szentirmai E., Kapás L., Krueger J.M. Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007, 292:R575-R585.
78. Szentirmai E., Kapás L., Sun Y., Smith R.G., Krueger J.M. Spontaneous sleep and homeostatic sleep regulation in ghrelin knockout mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007, 293:R510-R517.
79. Szentirmai E., Kapás L., Sun Y., Smith R.G., Krueger J.M. The preproghrelin gene is required for the normal integration of thermoregulation and sleep in mice. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:14069-14074.
80. Taheri S., Lin L., Austin D., Young T., Mignot E. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med. 2004, 1:e62.
81. Tschöp M., Smiley D.L., Heiman M.L. Ghrelin induces adiposity in rodents. Nature 2000, 407:908-913.
82. Weikel J.C., Wichniak A., Ising M., Brunner H., Friess E., Held K., Mathias S., Schmid D.A., Uhr M., Steiger A. Ghrelin promotes slow-wave sleep in humans. Am. J. Physiol. Endocrinol. Metab. 2003, 284:E407-E415.
83. Weikel J., Held K., Schmid D.A., Uhr M., Steiger A. Single case report: 100μg ghrelin at 22:00 increases distinctly hunger, food intake and nocturnal plasma levels of GH, ACTH and cortisol in a young man - evidence for dose-dependent effects of ghrelin on appetite?. Pharmacopsychiatry 2005, 38:284.
84. Wren A.M, Small C.J., Ward H.L., Murphy K.G., Dakin C.L., Taheri S., Kennedy A.R., Roberts G.H., Morgan D.G.A., Ghatei M.A., Bloom S.R. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000, 141:4325-4328.
85. Wren A.M., Seal L.J., Cohen M.A., Brynes A.E., Frost G.S., Murphy K.G., Dhillo W.S., Ghatei M.A., Bloom S.R. Ghrelin enhances appetite and increases food intake in humans. J. Clin. Endocrinol. Metab. 2001, 86:5992-5995.
86. Zhang J., Obál F., Zheng T., Fang J., Taishi P., Krueger J.M. Intrapreoptic microinjection of GHRH or its antagonist alters sleep in rats. J. Neurosci. 1999, 19:2187-2194.