Ghrelin receptor signaling: A promising therapeutic target for metabolic syndrome and cognitive dysfunction

CNS and Neurological Disorders - Drug Targets

Volumn 9, Issue 5, 2010, Pages 557-563

  Cong, Wei na ^a   Golden, Erin ^b   Pantaleo, Nick ^a   White, Caitlin M ^a   Maudsley, Stuart ^a   Martin, Bronwen ^a  

^a NATIONAL INSTITUTE ON AGING   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cognitive function; Energy balance; Ghrelin; Growth hormone secretagagogue receptor; Memory; Metabolic disorders; Neuroprotection; Obesity

Indexed keywords

GHRELIN; GHRELIN RECEPTOR; GLUCOSE; INSULIN;

APPETITE; ARTICLE; BRAIN FUNCTION; COGNITION; COGNITIVE DEFECT; DRUG TARGETING; ENERGY BALANCE; HUMAN; MEMORY; METABOLIC SYNDROME X; NEUROLOGIC DISEASE; NEUROPROTECTION; NONHUMAN; PROTEIN EXPRESSION;

EID: 77958615191     PISSN: 18715273     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152710793361513     Document Type: Article

References (81)

1. 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(6762), 656-660.
2. Guan, X.-M.; Yu, H.; Palyha, O.C.; McKee, K.K.; Feighner, S.D.; Sirinathsinghji, D.J.S.; Smith, R.G.; Van der Ploeg, L.H.T.; Howard, A.D. Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res. Mol. Brain Res., 1997, 48(1), 23-29.
3. Hou, Z.; Miao, Y.; Gao, L.; Pan, H.; Zhu, S. Ghrelin-containing neuron in cerebral cortex and hypothalamus linked with the DVC of brainstem in rat. Regul. Pept., 2006, 134(2-3), 126-131.
4. Flegal, K.M.; Carroll, M.D.; Ogden, C.L.; Curtin, L.R. Prevalence and trends in obesity among US adults, 1999-2008. JAMA, 2010, 303(3), 235-241.
5. Guh, D.P.; Zhang, W.; Bansback, N.; Amarsi, Z.; Birmingham, C.L.; Anis, A.H. The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysis. BMC Public Health, 2009, 9, 88.
6. Finkelstein, E.A.; Fiebelkorn, I.C.; Wang, G. State-level estimates of annual medical expenditures attributable to obesity. Obes. Res., 2004, 12(1), 18-24.
7. Thomas, V.S.; Darvesh, S.; MacKnight, C.; Rockwood, K. Estimating the prevalence of dementia in elderly people: a comparison of the Canadian study of health and aging and national population health survey approaches. Int. Psychogeriatr., 2001, 13(Supp 1), 169-175.
8. Peter, P.; Beatrix, S.; Eva, R.; Judit, T.; Karoly, R.; Aniko, S.; Zsolt, T. Ghrelin: a new peptide regulating the neurohormonal system, energy homeostasis and glucose metabolism. Diabetes Metab. Res. Rev., 2008, 24(5), 343-352.
9. Ariyasu, H.; Takaya, K.; Tagami, T.; Ogawa, Y.; Hosoda, K.; Akamizu, T.; Suda, M.; Koh, T.; Natsui, K.; Toyooka, S.; Shirakami, G.; Usui, T.; Shimatsu, A.; Doi, K.; Hosoda, H.; Kojima, M.; Kangawa, K.; Nakao, K. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J. Clin. Endocrinol. Metab., 2001, 86(10), 4753-4758.
10. Caminos, J.E.; Tena-Sempere, M.; Gaytan, F.; Sanchez-Criado, J.E.; Barreiro, M.L.; Nogueiras, R.; Casanueva, F.F.; Aguilar, E.; Dieguez, C. Expression of ghrelin in the cyclic and pregnant rat ovary. Endocrinology, 2003, 144(4), 1594-1602.
11. Fuglsang, J.; Gerald, L. Ghrelin in pregnancy and lactation. Vitam. Horm., 2008, 77, 259-284.
12. Mori, K.; Yoshimoto, A.; Takaya, K.; Hosoda, K.; Ariyasu, H.; Yahata, K.; Mukoyama, M.; Sugawara, A.; Hosoda, H.; Kojima, M.; Kangawa, K.; Nakao, K. Kidney produces a novel acylated peptide, ghrelin. FEBS Lett., 2000, 486(3), 213-216.
13. Korbonits, M.; Bustin, S.A.; Kojima, M.; Jordan, S.; Adams, E.F.; Lowe, D.G.; Kangawa, K.; Grossman, A. B. The Expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors. J. Clin. Endocrinol. Metab., 2001, 86(2), 881-887.
14. Volante, M.; AllIa, E.; Gugliotta, P.; Funaro, A.; Broglio, F.; Deghenghi, R.; Muccioli, G.; Ghigo, E.; Papotti, M. Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J. Clin. Endocrinol. Metab., 2002, 87(3), 1300-1308.
15. Lu, S.; Guan, J.L.; Wang, Q.P.; Uehara, K.; Yamada, S.; Goto, N.; Date, Y.; Nakazato, M.; Kojima, M.; Kangawa, K.; Shioda, S. Immunocytochemical observation of ghrelin-containing neurons in the rat arcuate nucleus. Neurosci. Lett., 2002, 321(3), 157-160.
16. Cowley, M.A.; Smith, R.G.; Diano, S.; Tschöp, M.; Pronchuk, N.; Grove, K.L.; Strasburger, C.J.; Bidlingmaier, M.; Esterman, M.; Heiman, M.L.; Garcia-Segura, L.M.; Nillni, E.A.; Mendez, P.; Low, M.J.; Sotonyi, P.; Friedman, J.M.; Liu, H.; Pinto, S.; Colmers, W.F.; Cone, R.D.; Horvath, T.L. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron, 2003, 37(4), 649-661.
17. Soares, J.B.; Roncon-Albuquerque, R.; Leite-Moreira, A. Ghrelin and ghrelin receptor inhibitors: agents in the treatment of obesity. Expert Opin. Ther. Targets, 2008, 12(9), 1177-1189.
18. McKee, K.K.; Palyha, O.C.; Feighner, S.D.; Hreniuk, D.L.; Tan, C.P.; Phillips, M. S.; Smith, R.G.; Van der Ploeg, L.H.T.; Howard, A.D. Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors. Mol. Endocrinol., 1997, 11(4), 415-423.
19. Feighner, S.D.; Tan, C.P.; McKee, K.K.; Palyha, O.C.; Hreniuk, D.L.; Pong, S.-S.; Austin, C. P.; Figueroa, D.; MacNeil, D.; Cascieri, M.A.; Nargund, R.; Bakshi, R.; Abramovitz, M.; Stocco, R.; Kargman, S.; O'Neill, G.; Van Der Ploeg, L.H.; Evans, J.; Patchett, A.A.; Smith, R.G.; Howard, A.D. Receptor for motilin identified in the human gastrointestinal system. Science, 1999, 284(5423), 2184-2188.
20. Gomez, R.; Lago, F.; Gomez-Reino, J.J.; Gualillo, O. Novel factors as therapeutic targets to treat diabetes. Focus on leptin and ghrelin. Expert Opin. Ther. Targets, 2009, 13(5), 583-591.
21. Nakazato, M.; Murakami, N.; Date, Y.; Kojima, M.; Matsuo, H.; Kangawa, K.; Matsukura, S. A role for ghrelin in the central regulation of feeding. Nature, 2001, 409(6817), 194-198.
22. Shimizu, Y.; Nagaya, N.; Teranishi, Y.; Imazu, M.; Yamamoto, H.; Shokawa, T.; Kangawa, K.; Kohno, N.; Yoshizumi, M. Ghrelin improves endothelial dysfunction through growth hormone-independent mechanisms in rats. Biochem. Biophys. Res. Commun., 2003, 310(3), 830-835.
23. Nagaya, N.; Moriya, J.; Yasumura, Y.; Uematsu, M.; Ono, F.; Shimizu, W.; Ueno, K.; Kitakaze, M.; Miyatake, K.; Kangawa, K. Effects of Ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation, 2004, 110(24), 3674-3679.
24. Masuda, Y.; Tanaka, T.; Inomata, N.; Ohnuma, N.; Tanaka, S.; Itoh, Z.; Hosoda, H.; Kojima, M.; Kangawa, K. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem. Biophys. Res. Commun., 2000, 276(3), 905-908.
25. Baldanzi, G.; Filigheddu, N.; Cutrupi, S.; Catapano, F.; Bonissoni, S.; Fubini, A.; Malan, D.; Baj, G.; Granata, R.; Broglio, F.; Papotti, M.; Surico, N.; Bussolino, F.; Isgaard, J.; Deghenghi, R.; Sinigaglia, F.; Prat, M.; Muccioli, G.; Ghigo, E.; Graziani, A. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J. Cell. Biol., 2002, 159(6), 1029-1037.
26. Li, W.G.; Gavrila, D.; Liu, X.; Wang, L.; Gunnlaugsson, S.; Stoll, L. L.; McCormick, M. L.; Sigmund, C. D.; Tang, C.; Weintraub, N. L. Ghrelin inhibits proinflammatory responses and nuclear factor-kappaB activation in human endothelial cells. Circulation, 2004, 109(18), 2221-2226.
27. Xia, Q.; Pang, W.; Pan, H.; Zheng, Y.; Kang, J.S.; Zhu, S.G. Effects of ghrelin on the proliferation and secretion of splenic T lymphocytes in mice. Regul. Pept., 2004, 122(3), 173-178.
28. Tschop, M.; Smiley, D.L.; Heiman, M.L. Ghrelin induces adiposity in rodents. Nature, 2000, 407(6806), 908-913.
29. Wren, A.M.; Small, C.J.; Abbott, C.R.; Dhillo, W.S.; Seal, L.J.; Cohen, M.A.; Batterham, R.L.; Taheri, S.; Stanley, S.A.; Ghatei, M.A.; Bloom, S.R. Ghrelin causes hyperphagia and obesity in rats. Diabetes, 2001, 50(11), 2540-2547.
30. 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(12), 5992-5995.
31. 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(8), 1714-1719.
32. Morton, G.J.; Cummings, D.E.; Baskin, D.G.; Barsh, G.S.; Schwartz, M.W. Central nervous system control of food intake and body weight. Nature, 2006, 443(7109), 289-295.
33. Chen, H.Y.; Trumbauer, M.E.; Chen, A.S.; Weingarth, D.T.; Adams, J.R.; Frazier, E.G.; Shen, Z.; Marsh, D.J.; Feighner, S.D.; Guan, X.M.; Ye, Z.; Nargund, R.P.; Smith, R.G.; Van der Ploeg, L.H.T.; Howard, A.D.; MacNeil, D.J.; Qian, S. Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology, 2004, 145(6), 2607-2612.
34. Toshinai, K.; Date, Y.; Murakami, N.; Shimada, M.; Mondal, M.S.; Shimbara, T.; Guan, J.-L.; Wang, Q.-P.; Funahashi, H.; Sakurai, T.; Shioda, S.; Matsukura, S.; Kangawa, K.; Nakazato, M. Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology, 2003, 144(4), 1506-1512.
35. Kola, B.; Farkas, I.; Christ-Crain, M.; Wittmann, G.B.; Lolli, F.; Amin, F.; Harvey-White, J.; Liposits, Z.; Kunos, G.; Grossman, A.B.; Fekete, C.; Korbonits, M.R. The orexigenic effect of ghrelin is mediated through central activation of the endogenous cannabinoid system. PLoS One, 2008, 3(3), e1797.
36. Dezaki, K.; Sone, H.; Yada, T. Ghrelin is a physiological regulator of insulin release in pancreatic islets and glucose homeostasis. Pharmacol. Ther., 2008, 118(2), 239-249.
37. McLaughlin, T.; Abbasi, F.; Lamendola, C.; Frayo, R.S.; Cummings, D.E. Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls. J. Clin. Endocrinol. Metab., 2004, 89(4), 1630-1635.
38. Broglio, F.; Arvat, E.; Benso, A.; Gottero, C.; Muccioli, G.; Papotti, M.; Lely, A.J.V.D.; Deghenghi, R.; Ghigo, E. Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J. Clin. Endocrinol. Metab., 2001, 86(10), 5083-5086.
39. Dezaki, K.; Hosoda, H.; Kakei, M.; Hashiguchi, S.; Watanabe, M.; Kangawa, K.; Yada, T. Endogenous Ghrelin in pancreatic islets restricts insulin release by attenuating Ca2+ signaling in beta-cells. Diabetes, 2004, 53(12), 3142-3151.
40. Katergari, S. A.; Milousis, A.; Pagonopoulou, O.; Asimakopoulos, B.; Nikolettos, N.K. Ghrelin in pathological conditions. Endocr. J., 2008, 55(3), 439-453.
41. Tschop, M.; Weyer, C.; Tataranni, P.A.; Devanarayan, V.; Ravussin, E.; Heiman, M.L. Circulating ghrelin levels are decreased in human obesity. Diabetes, 2001, 50(4), 707-709.
42. Shiiya, T.; Nakazato, M.; Mizuta, M.; Date, Y.; Mondal, M.S.; Tanaka, M.; Nozoe, S.-I.; Hosoda, H.; Kangawa, K.; Matsukura, S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J. Clin. Endocrinol. Metab., 2002, 87(1), 240-244.
43. Nogueiras, R.; Tschop, M.H.; Zigman, J.M. Central nervous system regulation of energy metabolism: ghrelin versus leptin. Ann. NY Acad. Sci., 2008, 1126, 14-19.
44. Cummings, D.E.; Weigle, D.S.; Frayo, R.S.; Breen, P.A.; Ma, M.K.; Dellinger, E.P.; Purnell, J.Q. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N. Engl. J. Med., 2002, 346(21), 1623-1630.
45. Hameed, S.; Dhillo, W.S.; Bloom, S.R. Gut hormones and appetite control. Oral Dis., 2009, 15(1), 18-26.
46. Tanaka, M.; Naruo, T.; Muranaga, T.; Yasuhara, D.; Shiiya, T.; Nakazato, M.; Matsukura, S.; Nozoe, S. Increased fasting plasma ghrelin levels in patients with bulimia nervosa. Eur. J. Endocrinol., 2002, 146(6), R1-R3.
47. Cummings, D.E.; Clement, K.; Purnell, J.Q.; Vaisse, C,; Foster, K.E.; Frayo, R.S.; Schwartz, M.W.; Basdevant, A.; Weigle, D.S. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat. Med., 2002, 8(7), 643-644.
48. Monteleone, P.; Martiadis, V.; Fabrazzo, M.; Serritella, C.; Maj, M. Ghrelin and leptin responses to food ingestion in bulimia nervosa: implications for binge-eating and compensatory behaviours. Psychol. Med., 2003, 33(8), 1387-1394.
49. Kojima, S.; Nakahara, T.; Nagai, N.; Muranaga, T.; Tanaka, M.; Yasuhara, D.; Masuda, A.; Date, Y.; Ueno, H.; Nakazato, M.; Naruo, T. Altered ghrelin and peptide YY responses to meals in bulimia nervosa. Clin. Endocrinol., 2005, 62(1), 74-78.
50. Gueorguiev, M.; Lecoeur, C.; Meyre, D.; Benzinou, M.; Mein, C.A.; Hinney, A.; Vatin, V.; Weill, J.; Heude, B.; Hebebrand, J.; Grossman, A.B.; Korbonits, M.; Froguel, P. Association studies on ghrelin and ghrelin receptor gene polymorphisms with obesity. Obesity, 2009, 17(4), 745-754.
51. Stunkard, A.J.; Allison, K.C. Two forms of disordered eating in obesity: binge eating and night eating. Int. J. Obes. Relat. Metab. Disord., 2003, 27(1), 1-12.
52. Allison, K.C.; Stunkard, A.J. Obesity and eating disorders. Psychiatr. Clin. N. Am., 2005, 28(1), 55-67.
53. Faith, M.S.; Berkowitz, R.I.; Stallings, V.A.; Kerns, J.; Storey, M.; Stunkard, A.J. Eating in the absence of hunger: a genetic marker for childhood obesity in prepubertal boys? Obesity, 2006, 14(1), 131-138.
54. Shimbara, T.; Mondai, M.S.; Kawagoe, T.; Toshinai, K.; Koda, S.; Yamaguchi, H.; Date, Y.; Nakazato, M. Central administration of ghrelin preferentially enhances fat ingestion. Neurosci. Lett., 2004, 369(1), 75-79.
55. Scacchi, M.; Ida Pincelli, A.; Cavagini, F. Nutritional status in the neuroendocrine control of growth hormone secretion: the model of anorexia nervosa. Front. Neuroendocrinol., 2003, 24(3), 200-224.
56. Tanaka, M.; Naruo, T.; Yasuhara, D.; Tatebe, Y.; Nagai, N.; Shiiya, T.; Nakazato, M.; Matsukura, S.; Nozoe, S. Fasting plasma ghrelin levels in subtypes of anorexia nervosa. Psychoneuroendocrinology, 2003, 28(7), 829-835.
57. de Krom, M. van der Schouw, Y.T.; Hendriks, J.; Ophoff, R.A.; van Gils, C.H.; Stolk, R.P.; Grobbee, D.E.; Adan. R. Common genetic variations in CCK, leptin, and leptin receptor genes are associated with specific human eating patterns. Diabetes, 2007, 56(1), 276-280.
58. Gueorguiev, M.; Lecoeur, C.; Meyre, D.; Benzinou, M.; Mein, C.A.; Hinney, A.; Vatin, V.; Weill, J.; Heude, B.; Hebebrand, J.; Grossman, A.B.; Korbonits, M.; Froguel, P. Association studies on ghrelin and ghrelin receptor gene polymorphisms with obesity. Obesity, 2009, 17(4), 745-754.
59. Carlini, V.P.; Monzón, M.E.; Varas, M.M.; Cragnolini, A.B.; Schiöth, 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(5), 739-743.
60. Carlini, V.P.; Varas, M.M.; Cragnolini, A.B.; Schiöth, 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(3), 635-641.
61. 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(3), 381-388.
62. Wortley, K.E.; del Rincon, J.P.; Murray, J.D.; Garcia, K.; Iida, K.; Thorner, M.O.; Sleeman, M.W. Absence of ghrelin protects against early-onset obesity. J. Clin. Invest., 2005, 115(12), 3573-3578.
63. Zigman, J.M.; Nakano, Y.; Coppari, R.; Balthasar, N.; Marcus, J.N.; Lee, C.E.; Jones, J.E.; Deysher, A.E.; Waxman, A.R.; White, R.D.; Williams, T.D.; Lachey, J.L.; Seeley, R.J.; Lowell, B.B.; Elmquist, J.K. Mice lacking ghrelin receptors resist the development of diet-induced obesity. J. Clin. Invest., 2005, 115(12), 3564-3572.
64. 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 (Berl.), 2009, 206(3), 415-427.
65. Moon, M.; Kim, S.; Hwang, L.; Park, S. Ghrelin regulates hippocampal neurogenesis in adult mice. Endocr. J., 2009, 56(3), 525-531.
66. Bredesen, D.E.; Rao, R.V.; Mehlen, P. Cell death in the nervous system. Nature, 2006, 443(7113), 796-802.
67. Jenner, P.; Olanow, C.W. The pathogenesis of cell death in Parkinson's disease. Neurology, 2006, 66(10 Suppl 4), S24-36.
68. Jiang, H.; Luan, Z.; Wang, J.; Xie, J. Neuroprotective effects of iron chelator Desferal on dopaminergic neurons in the substantia nigra of rats with iron-overload. Neurochem. Int., 2006, 49(6), 605-609.
69. Xie, J.X.; Jiang, H.; Chen, W.F.; Qian, Z.M. Dopamine release rather than content in the caudate putamen is associated with behavioral changes in the iron rat model of Parkinson's disease. Exp. Neurol., 2003, 182(2), 483-489.
70. Dauer, W.; Przedborski, S. Parkinson's disease: mechanisms and models. Neuron, 2003, 39(6), 889-909.
71. Hunot, S.; Hirsch, E.C. Neuroinflammatory processes in Parkinson's disease. Ann. Neurol., 2003, 53(Suppl 3), S49-S58.
72. Barnham, K.J.; Masters, C.L.; Bush, A.I. Neurodegenerative diseases and oxidative stress. Nat. Rev. Drug Discov., 2004, 3(3), 205-214.
73. Jiang, H.; Li, L.-J.; Wang, J.; Xie, J.-X. Ghrelin antagonizes MPTP-induced neurotoxicity to the dopaminergic neurons in mouse substantia nigra. Exp. Neurol., 2008, 212(2), 532-537.
74. Jiang, H.; Betancourt, L.; Smith, R.G. Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers. Mol. Endocrinol., 2006, 20(8), 1772-1785.
75. Andrews, Z.B.; Erion, D.; Beiler, R.; Liu, Z.W.; Abizaid, A.; Zigman, J.; Elsworth, J.D.; Savitt, J.M.; DiMarchi, R.; Tschoep, M.; Roth, R.H.; Gao, X.B.; Horvath, T.L. Ghrelin promotes and protects nigrostriatal dopamine function via a UCP2-dependent mitochondrial mechanism. J. Neurosci., 2009, 29(45), 14057-14065.
76. Hwang, S.; Moon, M.; Kim, S.; Hwang, L.; Ahn, K.J.; Park, S. Neuroprotective effect of ghrelin is associated with decreased expression of prostate apoptosis response-4. Endocr. J., 2009, 56(4), 609-617.
77. Liu, Y.; Chen, L.; Xu, X.; Vicaut, E.; Sercombe, R. Both ischemic preconditioning and ghrelin administration protect hippocampus from ischemia/reperfusion and upregulate uncoupling protein-2. BMC Physiol., 2009, 9, 17.
78. Miao, Y.; Xia, Q.; Hou, Z.; Zheng, Y.; Pan, H.; Zhu, S. Ghrelin protects cortical neuron against focal ischemia/reperfusion in rats. Biochem. Biophys. Res. Commun., 2007, 359(3), 795-800.
79. Xu, J.; Wang, S.; Lin, Y.; Cao, L.; Wang, R.; Chi, Z. Ghrelin protects against cell death of hippocampal neurons in pilocarpine-induced seizures in rats. Neurosci. Lett., 2009, 453(1),58-61.
80. Martin, B.; Mattson, M.P.; Maudsley, S. Caloric restriction and intermittent fasting: Two potential diets for successful brain aging. Ageing Res. Rev., 2006, 5(3), 332-353.
81. Martin, B.; Golden, E.; Keselman, A.; Stone, M.; Mattson, M.P.; Egan, J.M.; Maudsley S. Therapeutic perspectives for the treatment of Huntington's disease: treating the whole body. Histol. Histopathol., 2008, 23(2), 237-250.