Neuroactive peptides as putative mediators of antiepileptic ketogenic diets

Frontiers in Neurology

Volumn 5 APR, Issue , 2014, Pages

  Giordano, Carmela ^a   Marchiò, Maddalena ^a,b,c   Timofeeva, Elena ^d   Biagini, Giuseppe ^a,c  

^a UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

^b UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

^c NOCSAE Baggiovara Hospital   (Italy)

^d LAVAL UNIVERSITY   (Canada)

Author keywords

Adiponectin; Epilepsy; Fasting; Ghrelin; Ketogenic diet; Neuropeptide Y

Indexed keywords

4 AMINOBUTYRIC ACID; ADENOSINE; ADIPOCYTOKINE; ADIPONECTIN; AMYLIN; CHOLECYSTOKININ; CORTICOTROPIN RELEASING FACTOR; GALANIN; GHRELIN; GLUCAGON; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; GROWTH HORMONE RELEASING FACTOR; INSULIN; KETONE BODY; LEPTIN; NEUROPEPTIDE; NEUROPEPTIDE Y; OXYNTOMODULIN; PANCREAS POLYPEPTIDE; PEPTIDE HORMONE; PEPTIDE YY; POLYUNSATURATED FATTY ACID;

ANOREXIA; ANTICONVULSANT ACTIVITY; BRAIN PH; CACHEXIA; DIETARY INTAKE; ENERGY METABOLISM; EPILEPSY; GLUCOSE BLOOD LEVEL; HORMONE SYNTHESIS; KETOGENESIS; KETOGENIC DIET; LIPID METABOLISM; METABOLIC REGULATION; NERVE CELL NETWORK; NERVE EXCITABILITY; NEUROMODULATION; NEUROTRANSMISSION; NEUROTRANSMITTER RELEASE; PH; PROTEIN FUNCTION; PROTEIN SYNTHESIS; REVIEW; STARVATION; SYNAPSE; UPREGULATION;

EID: 84901008236     PISSN: None     EISSN: 16642295     Source Type: Journal    
DOI: 10.3389/fneur.2014.00063     Document Type: Review

References (225)

1. Berg AT, Baca CB, Loddenkemper T, Vickrey BG, Dlugos D. Priorities in pediatric epilepsy research: improving children's futures today. Neurology (2013) 81:1166-75. doi: 10.1212/WNL.0b013e3182a55fb9.
2. Perucca E, French J, Bialer M. Development of new antiepileptic drugs: challenges, incentives, and recent advances. Lancet Neurol (2007) 6:793-804. doi:10.1016/S1474-4422(07)70215-6.
3. Wiebe S, Blume WT, Girvin JP, Eliasziw M. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med (2001) 345:311-8. doi:10.1056/NEJM200108023450501.
4. Lim ME, Bowen JM, Snead OC, Elliott I, Donner E, Weiss SK, et al. Access to surgery for pediatric patients with medically refractory epilepsy: a systems analysis. Epilepsy Res (2013) 107:286-96. doi:10.1016/j.eplepsyres.2013.08.010.
5. Engel J Jr, McDermott MP, Wiebe S, Langfitt JT, Stern JM, Dewar S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA (2012) 307:922-30. doi:10.1001/jama.2012.220.
6. Schachter SC, Saper CB. Vagus nerve stimulation. Epilepsia (1998) 39:677-86. doi:10.1111/j.1528-1157.1998.tb01151.
7. Parker AP, Polkey CE, Binnie CD, Madigan C, Ferrie CD, Robinson RO. Vagal nerve stimulation in epileptic encephalopathies. Pediatrics (1999) 103:778-82. doi:10.1542/peds.103.4.778.
8. Carius A, Wintermantel A. Vagus nerve stimulation therapy in epilepsy patients: long-term outcome and adverse effects: a retrospective analysis. Nervenarzt (2013) 84:1473-85. doi:10.1007/s00115-013-3923-4.
9. Klinkenberg S, van den Bosch CN, Majoie HJ, Aalbers MW, Leenen L, Hendriksen J, et al. Behavioural and cognitive effects during vagus nerve stimulation in children with intractable epilepsy-a randomized controlled trial. Eur J Paediatr Neurol (2013) 17:82-90. doi:10.1016/j.ejpn.2012.07.003.
10. Morris III GL, Gloss D, Buchhalter J, Mack JK, Nickels K, Harden C. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy. Neurology (2013) 81:1453-9. doi:10.1212/WNL.0b013e3182a393d1.
11. Skarpaas TL, Morrell MJ. Intracranial stimulation therapy for epilepsy. Neurotherapeutics (2009) 6:238-43. doi:10.1016/j.nurt.2009.01.022.
12. Kerrigan JF, Litt B, Fisher RS, Cranstoun S, French JA, Blum DE, et al. Electrical stimulation of the anterior nucleus of the thalamus for the treatment of intractable epilepsy. Epilepsia (2004) 45:346-54. doi:10.1111/j.0013-9580.2004.01304.x.
13. Oommen J, Morrell M, Fisher RS. Experimental electrical stimulation therapy for epilepsy. Curr Treat Options Neurol (2005) 7:261-71. doi:10.1007/s11940-005-0036-9.
14. Cordella R, Acerbi F, Marras CE, Carozzi C, Vailati D, Saini M, et al. Risk of seizures during intraoperative electrocortical stimulation of brain motor areas: a retrospective study on 50 patients. Neurol Sci (2013) 34:63-70. doi:10.1007/s10072-012-0968-2.
15. Lefevre F, Aronson N. Ketogenic diet for the treatment of refractory epilepsy in children: a systematic review of efficacy. Pediatrics (2000) 105:E46. doi:10.1542/peds.105.4.e46.
16. Coppola G, Veggiotti P, Cusmai R, Bertoli S, Cardinali S, Dionisi-Vici C, et al. The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience. Epilepsy Res (2002) 48:221-7. doi:10.1016/S0920-1211(01)00315-1.
17. Levy RG, Cooper PN, Giri P. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev (2012) 3:CD001903. doi:10.1002/14651858.CD001903.
18. Freeman JM, Vining EP, Pillas DJ, Pyzik PL, Casey JC, Kelly LM. The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children. Pediatrics (1998) 102:1358-63. doi:10.1542/peds.102.6.1358.
19. Hartman AL, Vining EP. Clinical aspects of the ketogenic diet. Epilepsia (2007) 48:31-42. doi:10.1111/j.1528-1167.2007.00914.x.
20. Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol (2008) 7:500-6. doi:10.1016/S1474-4422(08)70092-9.
21. Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, et al. A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia (2009) 50:1109-17. doi:10.1111/j.1528-1167.2008.01870.
22. KossoffEH, Zupec-Kania BA, Amark PE. Optimal clinical management of children receiving the ketogenic diet: recommendations of the international ketogenic diet study group. Epilepsia (2009) 50:304-17. doi:10.1111/j.1528-1167.2008.01765.x.
23. Wilder RM. The effects of ketonemia on the course of epilepsy. Mayo Clin Bull (1921) 2:307-8.
24. Stafstrom CE. Dietary approaches to epilepsy treatment: old and new options on the menu. Epilepsy Curr (2004) 4:215-22. doi:10.1111/j.1535-7597.2004.46001.x.
25. KossoffEH, McGrogan JR, Bluml RM, Pillas DJ, Rubenstein JE, Vining EP. A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy. Epilepsia (2006) 47:421-4. doi:10.1111/j.1528-1167.2006.00438.x.
26. Chapman KE, Kim DY, Rho JM, Ng YT, Kerrigan JF. Ketogenic diet in the treatment of seizures associated with hypothalamic hamartomas. Epilepsy Res (2011) 94:218-21. doi:10.1016/j.eplepsyres.2011.02.004.
27. Huttenlocher PR, Wilbourn AJ, Signore JM. Medium-chain triglycerides as a therapy for intractable childhood epilepsy. Neurology (1971) 21:1097-103. doi:10.1212/WNL.21.11.1097.
28. Atkins RC. Dr Atkins' New Diet Revolution. New York, NY: David McKay Inc Publishers (1972).
29. Pfeifer HH, Thiele EA. Low-glycemic-index treatment: a liberalized ketogenic diet for treatment of intractable epilepsy. Neurology (2005) 65:1810-2. doi:10.1212/01.wnl.0000187071.24292.9e.
30. Schwartz MW, Woods SC, Porte DJ, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature (2000) 404:661-71. doi:10.1038/35007534.
31. Gilbert DL, Pyzik PL, Freeman JM. The ketogenic diet: seizure control correlates better with serum β-hydroxybutyrate than with urine ketones. J Child Neurol (2000) 15:787-90. doi:10.1177/088307380001501203.
32. Bough KJ, Matthews PJ, Eagles DA. A ketogenic diet has different effects upon seizures induced by maximal electroshock and by pentylenetetrazole infusion. Epilepsy Res (2000) 38:105-14. doi:10.1016/S0920-1211(99)00079-0.
33. Seo JH, Lee YM, Lee JS, Kang HC, Kim HD. Efficacy and tolerability of the ketogenic diet according to lipid:nonlipid ratios-comparison of 3:1 with 4:1 diet. Epilepsia (2007) 48:801-5. doi:10.1111/j.1528-1167.2007.01025.x.
34. Seyfried BT, Mantis JG, Todorova MT, Greene AE. Dietary management of epilepsy: role of glucose and ketone bodies. In: Schwartzkroin PA, editor. The Encyclopedia of Basic Epilepsy Research (Vol. 2). San Diego, CA: Elsevier Press/Academic Press (2009). p. 687-93.
35. Appleton DB, DeVivo DC. An animal model for the ketogenic diet. Epilepsia (1974) 15:211-27. doi:10.1111/j.1528-1157.1974.tb04943.x.
36. Pan JW, de Graaf RA, Petersen KF, Shulman GI, Hetherington HP, Rothman DL. [2,4-13C2]-β-hydroxybutyrate metabolism in human brain. J Cereb Blood Flow Metab (2002) 22:890-8. doi:10.1097/00004647-200207000-00014.
37. McNally MA, Hartman AL. Ketone bodies in epilepsy. J Neurochem (2012) 121:28-35. doi:10.1111/j.1471-4159.2012.07670.
38. van Delft R, Lambrechts D, Verschuure P, Hulsman J, Majoie M. Blood beta-hydroxybutyrate correlates better with seizure reduction due to ketogenic diet than do ketones in the urine. Seizure (2010) 19:36-9. doi:10.1016/j.seizure.2009.10.009.
39. Likhodii SS, Musa K, Mendonca A, Dell C, Burnham WM, Cunnane SC. Dietary fat, ketosis, and seizure resistance in rats on the ketogenic diet. Epilepsia (2000) 41:1400-10. doi:10.1111/j.1528-1157.2000.tb00115.x.
40. Harney JP, Madara J, I'Anson H. Effects of acute inhibition of fatty acid oxidation on latency to seizure and concentrations of β hydroxybutyrate in plasma of rats maintained on calorie restriction and/or the ketogenic diet. Epilepsy Res (2002) 49:239-46. doi:10.1016/S0920-1211(02)00046-3.
41. Rho JM, White HS, Anderson G, Donevan S. Acetoacetate, acetone, and dibenzylamine (a contaminant in L-(+)-β-hydroxybutyrate) exhibit direct anticonvulsant actions in vivo. Epilepsia (2002) 43:358-61. doi:10.1046/j.1528-1157.2002.47901.x.
42. Samoilova M, Weisspapir M, Abdelmalik P, Velumian AA, Carlen PL. Chronic in vitro ketosis is neuroprotective but not anti-convulsant. J Neurochem (2010) 113:826-35. doi:10.1111/j.1471-4159.2010.
43. Likhodii SS, Serbanescu I, Cortez MA, Murphy P, Snead OC, Burnham WM. Anticonvulsant properties of acetone, a brain ketone elevated by the ketogenic diet. Ann Neurol (2003) 54:219-26. doi:10.1002/ana.10634.
44. Gasior M, French A, Joy MT, Tang RS, Hartman AL, Rogawski MA. The anticonvulsant activity of acetone, the major ketone body in the ketogenic diet, is not dependent on its metabolites acetol, 1,2-propanediol, methylglyoxal, or pyruvic acid. Epilepsia (2007) 48:793-800. doi:10.1111/j.1528-1167.2007.01026.x.
45. Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia (2007) 48:43-58. doi:10.1111/j.1528-1167.2007.00915.x.
46. Nylen K, Likhodii SS, Hum KM, Burnham WM. A ketogenic diet and diallyl sulfide do not elevate afterdischarge thresholds in adult kindled rats. Epilepsy Res (2006) 71:23-31. doi:10.1016/j.eplepsyres.2006.05.008.
47. Seymour KJ, Bluml S, Sutherling J, Sutherling W, Ross BD. Identification of cerebral acetone by 1H-MRS in patients with epilepsy controlled by ketogenic diet. MAGMA (1999) 8:33-42. doi:10.1007/BF02590633.
48. Nordli DR Jr, De Vivo DC. The ketogenic diet revisited: back to the future. Epilepsia (1997) 38:743-9. doi:10.1111/j.1528-1157.1997.tb01460.x.
49. Wada K, Kiryu K, Kawata Y, Chiba T, Mizuno K, Okada M, et al. Prognosis and clinical features of intractable epilepsy: a prospective study. Psychiatry Clin Neurosci (1997) 51:233-5. doi:10.1111/j.1440-1819.1997.tb02589.x.
50. Todorova MT, Tandon P, Madore RA, Stafstrom CE, Seyfried TN. The ketogenic diet inhibits epileptogenesis in EL mice: a genetic model for idiopathic epilepsy. Epilepsia (2000) 41:933-40. doi:10.1111/j.1528-1157.2000.tb00275.x.
51. Hartman AL, Gasior M, Vining EPG, Rogawski MA. The neuropharmacology of the ketogenic diet. Pediatr Neurol (2007) 36:281-92. doi:10.1016/j.pediatrneurol.2007.02.008.
52. Hartman AL, Lyle M, Rogawski MA, Gasior M. Efficacy of the ketogenic diet in the 6-Hz seizure test. Epilepsia (2008) 49:334-9. doi:10.1111/j.1528-1167.2007.01430.x.
53. Uhlemann ER, Neims AH. Anticonvulsant properties of the ketogenic diet in mice. J Pharmacol Exp Ther (1972) 180:231-8.
54. Mahoney AW, Hendricks DG, Bernhard N, Sisson DV. Fasting and ketogenic diet effects on audiogenic seizures susceptibility of magnesium deficient rats. Pharmacol Biochem Behav (1983) 18:683-7. doi:10.1016/0091-3057(83)90006-0.
55. Hori A, Tandon P, Holmes GL, Stafstrom CE. Ketogenic diet: effects on expression of kindled seizures and behavior in adult rats. Epilepsia (1997) 38:750-8. doi:10.1111/j.1528-1157.1997.tb01461.x.
56. Muller-Schwarze AB, Tandon P, Liu Z, Yang Y, Holmes GL, Stafstrom CE. Ketogenic diet reduces spontaneous seizures and mossy fiber sprouting in the kainic acid model. Neuroreport (1999) 10:1517-22. doi:10.1097/00001756-199905140-00023.
57. Rho JM, Kim DW, Robbins CA, Anderson GD, Schwartzkroin PA. Age-dependent differences in flurothyl seizure sensitivity in mice treated with a ketogenic diet. Epilepsy Res (1999) 37:233-40. doi:10.1016/S0920-1211(99)00068-6.
58. Bough KJ, Eagles DA. A ketogenic diet increases the resistance to pentylenetetrazole-induced seizures in the rat. Epilepsia (1999) 40:138-43. doi:10.1111/j.1528-1157.1999.tb02066.x.
59. Mantis JG, Centeno NA, Todorova MT, McGowan R, Seyfried TN. Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies. Nutr Metab (2004) 1:11. doi:10.1186/1743-7075-1-11.
60. Thavendiranathan P, Chow C, Cunnane S, McIntyre Burnham W. The effect of the "classic" ketogenic diet on animal seizure models. Brain Res (2003) 959:206-13. doi:10.1016/S0006-8993(02)03744-7.
61. Nylen K, Velazquez JL, Likhodii SS, Cortez MA, Shen L, Leshchenko Y, et al. A ketogenic diet rescues the murine succinic semialdehyde dehydrogenase deficient phenotype. Exp Neurol (2008) 210:449-57. doi:10.1016/j.expneurol.2007.11.015.
62. Dahlin M, Elfving A, Ungerstedt U, Amark P. The ketogenic diet influences the levels of excitatory and inhibitory amino acids in the CSF in children with refractory epilepsy. Epilepsy Res (2005) 64:115-25. doi:10.1016/j.eplepsyres.2005.03.008.
63. YudkoffM, Daikhin Y, Nissim I, Lazarow A, Nissim I. Ketogenic diet, brain glutamate metabolism and seizure control. Prostaglandins Leukot Essent Fatty Acids (2004) 70:277-85. doi:10.1016/j.plefa.2003.07.005.
64. Melo TM, Nehlig A, Sonnewald U. Neuronal-glial interactions in rats fed a ketogenic diet. Neurochem Int (2006) 48:498-507. doi:10.1016/j.neuint.2005.12.037.
65. Bough KJ, Schwartzkroin PA, Rho JM. Calorie restriction and ketogenic diet diminish neuronal excitability in rat dentate gyrus in vivo. Epilepsia (2003) 44:752-60. doi:10.1046/j.1528-1157.2003.55502.x.
66. Juge N, Gray JA, Omote H, Miyaji T, Inoue T, Hara C, et al. Metabolic control of vesicular glutamate transport and release. Neuron (2010) 68:99-112. doi:10.1016/j.neuron.2010.09.002.
67. Ma W, Berg J, Yellen G. Ketogenic diet metabolites reduce firing in central neurons by opening KATP channels. J Neurosci (2007) 27:3618-25. doi:10.1523/JNEUROSCI.0132-07.2007.
68. Kawamura M Jr, Ruskin DN, Masino SA. Metabolic autocrine reguation of neurons involves cooperation among pannexin hemichannels, adenosine receptors, and KATP channels. J Neurosci (2010) 30:3886-95. doi:10.1523/JNEUROSCI.0055-10.2010.
69. Tanner GR, Lutas A, Martínez-François JR, Yellen G. Single KATP channel opening in response to action potential firing in mouse dentate granule neurons. J Neurosci (2011) 31:8689-96. doi:10.1523/JNEUROSCI.5951-10.2011.
70. Koranda JL, Ruskin DN, Masino SA, Blaise JH. A ketogenic diet reduces long-term potentiation in the dentate gyrus of freely behaving rats. J Neurophysiol (2011) 106:662-6. doi:10.1152/jn.00001.2011.
71. DeVivo DC, Leckie MP, Ferrendelli JS, McDougal DB. Chronic ketosis and cerebral metabolism. Ann Neurol (1978) 3:331-7. doi:10.1002/ana.410030410.
72. Bough KJ, Wetherington J, Hassel B, Pare JF, Gawryluk JW, Greene JG. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol (2006) 60:223-35. doi:10.1002/ana.20899.
73. Nylen K, Likhodii S, Burnham WM. The ketogenic diet: proposed mechanisms of action. Neurotherapeutics (2009) 6:402-5. doi:10.1016/j.nurt.2009.01.021.
74. Lennox WG, Cobb S. Studies in epilepsy VIII. The clinical effect of fasting. Arch Neurol Psychiatry (1928) 20:771-9. doi:10.1001/archneurpsyc.1928.02210160112009.
75. Al-Mudallal AS, LaManna JC, Lust WD, Harik SI. Diet-induced ketosis does not cause cerebral acidosis. Epilepsia (1996) 37:258-61. doi:10.1111/j.1528-1157.1996.tb00022.x.
76. Vamecq J, Vallée L, Lesage F, Gressens P, Stables JP. Antiepileptic popular ketogenic diet: emerging twists in an ancient story. Prog Neurobiol (2005) 75:1-28. doi:10.1016/j.pneurobio.2004.11.003.
77. Cullingford TE. The ketogenic diet; fatty acids, fatty acid-activated receptors and neurological disorders. Prostaglandins Leukot Essent Fatty Acids (2004) 70:253-64. doi:10.1016/j.plefa.2003.09.008.
78. Masino SA, Geiger JD. Are purines mediators of the anticonvulsant/neuroprotective effects of ketogenic diets? Trends Neurosci (2008) 31:273-8. doi:10.1016/j.tins.2008.02.009.
79. Masino SA, Theofilas P, Li T, Ruskin DN, Fredholm BB, Geiger JD, et al. A ketogenic diet suppresses seizures in mice through adenosine A1 receptors. J Clin Invest (2011) 121:2679-83. doi:10.1172/JCI57813.
80. Giorgi FS, Pizzanelli C, Biagioni F, Murri L, Fornai F. The role of norepinephrine in epilepsy: from the bench to the bedside. Neurosci Biobehav Rev (2004) 28:507-24. doi:10.1016/j.neubiorev.2004.06.008.
81. Kaminski RM, Shippenberg TS, Jeffrey MW, Rocha BA. Genetic deletion of the norepinephrine transporter decreases vulnerability to seizures. Neurosci Lett (2005) 382:51-5. doi:10.1016/j.neulet.2005.02.056.
82. Szot P, Weinshenker D, Rho JM, Storey TW, Schwartzkroin PA. Norepinephrine is required for the anticonvulsant effect of the ketogenic diet. Brain Res (2001) 129:211-4. doi:10.1016/S0165-3806(01)00213-9.
83. Hökfelt T, Mutt V. Neuropeptides. In: Adelman G, Smith BH, editors. Encyclopedia of Neuroscience (Vol. 2). Amsterdam: Elsevier (1999). p. 1423-9.
84. De Wied D, Sigling HO. Neuropeptides involved in the pathophysiology of schizophrenia and major depression. Neurotox Res (2002) 4:453-68. doi:10.1080/10298420290031432.
85. Simonato M. Gene therapy for epilepsy. Epilepsy Behav (2014). doi:10.1016/j.yebeh.2013.09.013.
86. Dobolyi A, Kekesi KA, Juhasz G, Szekely AD, Lovas G, Kovacs Z. Receptors of peptides as therapeutic targets in epilepsy research. Curr Med Chem (2014) 21:764-87. doi:10.2174/0929867320666131119154018.
87. Agnati LF, Cortelli P, Biagini G, Bjelke B, Fuxe K. Different classes of volume transmission signals exist in the central nervous system and are affected by metabolic signals, temperature gradients and pressure waves. Neuroreport (1994) 6:9-12. doi:10.1097/00001756-199412300-00004.
88. Ludwig M, Leng G. Dendritic peptide release and peptide-dependent behaviours. Nat Rev Neurosci (2006) 7:126-36. doi:10.1038/nrn1845.
89. Tallent MK. Presynaptic inhibition of glutamate release by neuropeptides: use-dependent synaptic modification. Results Probl Cell Differ (2008) 44:177-200. doi:10.1007/400_2007_037.
90. Fuxe K, Li XM, Bjelke B, Hedlund PB, Biagini G, Agnati LF. Possible mechanisms for the powerful actions of neuropeptides. Ann N Y Acad Sci (1994) 739:42-59. doi:10.1111/j.1749-6632.1994.tb19806.x.
91. Hökfelt T, Broberger C, Xu ZQ, Sergeyev V, Ubink R, Diez M. Neuropeptides-an overview. Neuropharmacology (2000) 39:1337-56. doi:10.1016/S0028-3908(00)00010-1.
92. Gil-Campos M, Aguilera CM, Canete R, Gil A. Ghrelin: a hormone regulating food intake and energy homeostasis. Br J Nutr (2006) 96:201-26. doi:10.1079/BJN20061787.
93. Bjorbaek C, Kahn BB. Leptin signalling in the central nervous system and the periphery. Recent Prog Horm Res (2004) 59:305-31. doi:10.1210/rp.59.1.305.
94. Acuna-Goycolea C, van den Pol AN. Neuroendocrine proopiomelanocortin neurons are excited by hypocretin/orexin. J Neurosci (2009) 29:1503-13. doi:10.1523/JNEUROSCI.5147-08.2009.
95. Hamilton TJ, Xapelli S, Michaelson SD, Larkum ME, Colmers WF. Modulation of distal calcium electrogenesis by neuropeptide Y1 receptors inhibits neorortical long-term depression. J Neurosci (2013) 33:11184-93. doi:10.1523/JNEUROSCI.5595-12.2013.
96. Heilig M, Koob GF, Ekman R, Britton KT. Corticotropin-releasing factor and neuropeptide Y: role in emotional integration. Trends Neurosci (1994) 17:80-5. doi:10.1016/0166-2236(94)90079-5.
97. Ögren SO, Kuteeva E, Hökfelt T, Kehr J. Galanin receptor antagonists: a potential novel pharmacological treatment for mood disorders. CNS Drugs (2006) 20:633-54. doi:10.2165/00023210-200620080-00003.
98. Schwarzer C. 30 Years of dynorphins-new insights on their functions in neuropsychiatric diseases. Pharmacol Ther (2009) 123:353-70. doi:10.1016/j.pharmthera.2009.05.006.
99. Muurahainen N, KissileffHR, Derogatis AJ, Pi-Sunyer FX. Effects of cholecystokinin-octapeptide (CCK-8) on food intake and gastric emptying in man. Physiol Behav (1988) 44:645-9. doi:10.1016/0031-9384(88)90330-7.
100. Little TJ, Horowitz M, Feinle-Bisset C. Role of cholecystokinin in appetite control and body weight regulation. Obes Rev (2005) 6:297-306. doi:10.1111/j.1467-789X.2005.00212.x.
101. Flint A, Raben A, Astrup A. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest (1998) 101:515-20. doi:10.1172/JCI990.
102. Gallwitz B. Anorexigenic effects of GLP-1 and its analogues. Handb Exp Pharmacol (2012) 209:185-207. doi:10.1007/978-3-642-24716-3_8.
103. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature (2002) 418:650-4. doi:10.1038/nature00887.
104. Karra E, Chandarana K, Batterham RL. The role of peptide YY in appetite regulation and obesity. J Physiol (2009) 587:19-25. doi:10.1113/jphysiol.2008.164269.
105. Cohen MA, Ellis SM, Le Roux CW, Batterham RL, Park A, Patterson M, et al. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab (2003) 88:4696-701. doi:10.1210/jc.2003-030421.
106. Dakin CL, Small CJ, Batterham RL, Neary NM, Cohen MA, Patterson M, et al. Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology (2004) 145:2687-95. doi:10.1210/en.2003-1338.
107. Batterham RL, Le Roux CW, Cohen MA, Park AJ, Ellis SM, Patterson M. Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab (2003) 88:3989-92. doi:10.1210/jc.2003-030630.
108. Hankir MK, Parkinson JR, Minnion JS, Addison ML, Bloom SR, Bell JD. Peptide YY 3-36 and pancreatic polypeptide differentially regulate hypothalamic neuronal activity in mice in vivo as measured by manganese-enhanced magnetic resonance imaging. J Neuroendocrinol (2011) 23:371-80. doi:10.1111/j.1365-2826.2011.02111.
109. Geary N. Pancreatic glucagon signals postprandial satiety. Neurosci Biobehav Rev (1990) 14:323-38. doi:10.1016/S0149-7634(05)80042-9.
110. Porte D Jr, Woods SC. Regulation of food intake and body weight in insulin. Diabetologia (1981) 20:274-80. doi:10.1007/BF00254493.
111. Werther GA, Hogg A, Oldfield BJ, McKinley MJ, Figdor R, Allen AM, et al. Localization and characterization of insulin receptors in rat brain and pituitary gland using in vitro autoradiography and computerized densitometry. Endocrinology (1987) 121:1562-70. doi:10.1210/endo-121-4-1562.
112. Cline MA, Nandar W, Smith ML, Pittman BH, Kelly M, Rogers JO. Amylin causes anorexigenic effects via the hypothalamus and brain stem in chicks. Regul Pept (2008) 146:140-6. doi:10.1016/j.regpep.2007.09.003.
113. Fulton S, Woodside B, Shizgal P. Modulation of brain reward circuitry by leptin. Science (2000) 287:125-8. doi:10.1126/science.287.5450.125.
114. Schwartz MW. Central nervous system regulation of food intake. Obesity (2006) 14(Suppl 2):1s-8s. doi:10.1038/oby.2006.275.
115. Qi Y, Takahashi N, Hileman SM, Patel HR, Berg AH, Pajvani UB, et al. Adiponectin acts in the brain to decrease body weight. Nat Med (2014) 10:524-9. doi:10.1038/nm1029.
116. Tovar S, Nogueiras R, Tung LY, Castañeda TR, Vázquez MJ, Morris A, et al. Central administration of resistin promotes short-term satiety in rats. Eur J Endocrinol (2005) 153:R1-R5. doi:10.1530/eje.1.01999.
117. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab (2001) 86:5992-5. doi:10.1210/jc.86.12.5992.
118. Naleid AM, Grace MK, Cummings DE, Levine AS. Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens. Peptides (2005) 26:2274-9. doi:10.1016/j.peptides.2005.04.025.
119. Portelli J, Michotte Y, Smolders I. Ghrelin: an emerging new anticonvulsant neuropeptide. Epilepsia (2012) 53:585-95. doi:10.1111/j.1528-1167.2012.03423.
120. Kinzig KP, Taylor RJ. Maintenance on a ketogenic diet: voluntary exercise, adiposity and neuroendocrine effects. Int J Obes (2009) 33:824-30. doi:10.1038/ijo.2009.109.
121. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, et al. Role of leptin in the neuroendocrine response to fasting. Nature (1996) 382:250-2. doi:10.1038/382250a0.
122. Oswiecimska J, Ziora K, Geisler G, Broll-Waska K. Prospective evaluation of leptin and neuropeptide Y (NPY) serum levels in girls with anorexia nervosa. Neuro Endocrinol Lett (2005) 26:301-4.
123. Monteleone P, Castaldo E, Maj M. Neuroendocrine dysregulation of food intake in eating disorders. Regul Pept (2008) 149:39-50. doi:10.1016/j.regpep.2007.10.007.
124. Hayes MR, Miller CK, Ulbrecht JS, Mauger JL, Parker-Klees L, Gutschall MD, et al. A carbohydrate-restricted diet alters gut peptides and adiposity signals in men and women with metabolic syndrome. J Nutr (2007) 137:1944-50.
125. Thio LL, Erbayat-Altay E, Rensing N, Yamada KA. Leptin contributes to slower weight gain in juvenile rodents on a ketogenic diet. Pediatr Res (2006) 60:413-7. doi:10.1203/01.pdr.0000238244.54610.27.
126. Honors MA, Davenport BM, Kinzig KP. Effects of consuming a high carbohydrate diet after eight weeks of exposure to a ketogenic diet. Nutr Metab (2009) 6:46. doi:10.1186/1743-7075-6-46.
127. Badman MK, Kennedy AR, Adams AC, Pissios P, Maratos-Flier E. A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss. Am J Physiol Endocrinol Metab (2009) 297:E1197-204. doi:10.1152/ajpendo.00357.
128. Fery F, Bourdoux P, Christophe J, Balasse EO. Hormonal and metabolic changes induced by an isocaloric isoproteinic ketogenic diet in healthy subjects. Diabete Metab (1982) 8:299-305.
129. Brichard SM, Delporte ML, Lambert M. Adipocytokines in anorexia nervosa: a review focusing on leptin and adiponectin. Horm Metab Res (2003) 35:337-42. doi:10.1055/s-2003-41353.
130. Chaolu H, Asakawa A, Ushikai M, Li YX, Cheng KC, Li JB. Effect of exercise and high-fat diet on plasma adiponectin and nesfatin levels in mice. Exp Ther Med (2011) 2:2369-73. doi:10.3892/etm.2011.199.
131. Bosy-Westphal A, Brabant G, Haas V, Onur S, Paul T, Nutzinger D. Determinants of plasma adiponectin levels in patients with anorexia nervosa examined before and after weight gain. Eur J Nutr (2005) 44:355-9. doi:10.1007/s00394-005-0533-3.
132. Tagami T, Satoh N, Usui T, Yamada K, Shimatsu A, Kuzuya H. Adiponectin in anorexia nervosa and bulimia nervosa. J Clin Endocrinol Metab (2004) 89:1833-7. doi:10.1210/jc.2003-031260.
133. Tabb K, Szot P, White SS, Liles LC, Weinshenker D. The ketogenic diet does not alter brain expression of orexigenic neuropeptides. Epilepsy Res (2004) 62:35-9. doi:10.1016/j.eplepsyres.2004.08.002.
134. Shiraev T, Chen H, Morris MJ. Differential effects of restricted versus unlimited high-fat feeding in rats on fat mass, plasma hormones and brain appetite regulators. J Neuroendocrinol (2009) 21:602-9. doi:10.1111/j.1365-2826.2009.01877.
135. Baranowska B, Wolinska-Witort E, Wasilewska-Dziubinska E, Roguski K, Chmielowska M. Plasma leptin, neuropeptide Y (NPY) and galanin concentrations in bulimia nervosa and in anorexia nervosa. Neuro Endocrinol Lett (2001) 22:356-8.
136. Gundlach AL. Galanin/GALP and galanin receptors: role in central control of feeding, body weight/obesity and reproduction? Eur J Pharmacol (2002) 440:255-68. doi:10.1016/S0014-2999(02)01433-4.
137. De Marinis L, Mancini A, Valle D, Bianchi A, Gentilella R, Milardi D, et al. Effects of galanin on growth hormone and prolactin secretion in anorexia nervosa. Metabolism (2000) 49:155-9. doi:10.1016/S0026-0495(00)91091-6.
138. Kinzig KP, Scott KA, Hyun J, Bi S, Moran TH. Altered hypothalamic signaling and responses to food deprivation in rats fed a low-carbohydrate diet. Obes Res (2005) 13:1672-82. doi:10.1038/oby.2005.205.
139. Nakahara T, Kojima S, Tanaka M, Yasuhara D, Harada T, Sagiyama K, et al. Incomplete restoration of the secretion of ghrelin and PYY compared to insulin after food ingestion following weight gain in anorexia nervosa. J Psychiatr Res (2007) 41:814-20. doi:10.1016/j.jpsychires.2006.07.021.
140. Tanaka M, Naruo T, Yasuhara D, Tatebe Y, Nagai N, Shiiya T, et al. Fasting plasma ghrelin levels in subtypes of anorexia nervosa. Psychoneuroendocrinology (2003) 28:829-35. doi:10.1016/S0306-4530(02)00066-5.
141. Otto B, Tschop M, Fruhauf E, Heldwein W, Fichter M, Otto C, et al. Postprandial ghrelin release in anorectic patients before and after weight gain. Psychoneuroendocrinology (2005) 30:577-81. doi:10.1016/j.psyneuen.2005.01.009.
142. Cheng CM, Kelley B, Wang J, Strauss D, Eagles DA, Bondy CA. A ketogenic diet increases brain insulin-like growth factor receptor and glucose transporter gene expression. Endocrinology (2003) 144:2676-82. doi:10.1210/en.2002-0057.
143. Misra M, Klibanski A. Neuroendocrine consequences of anorexia nervosa in adolescents. Endocr Dev (2010) 17:197-214. doi:10.1159/000262540.
144. Ueno N, Asakawa A, Satoh Y, Inui A. Increased circulating cholecystokinin contributes to anorexia and anxiety behavior in mice overexpressing pancreatic polypeptide. Regul Pept (2007) 141:8-11. doi:10.1016/j.regpep.2006.12.019.
145. Duca FA, Zhong L, Covasa M. Reduced CCK signaling in obese-prone rats fed a high fat diet. Horm Behav (2013) 64:812-7. doi:10.1016/j.yhbeh.2013.09.004.
146. Fujimoto S, Inui A, Kiyota N, Seki W, Koide K, Takamiya S, et al. Increased cholecystokinin and pancreatic polypeptide responses to a fat-rich meal in patients with restrictive but not bulimic anorexia nervosa. Biol Psychiatry (1997) 41:1068-70. doi:10.1016/S0006-3223(97)00044-9.
147. Keel PK, Wolfe BE, Liddle RA, De Young KP, Jimerson DC. Clinical features and physiological response to a test meal in purging disorder and bulimia nervosa. Arch Gen Psychiatry (2007) 64:1058-66. doi:10.1001/archpsyc.64.9.1058.
148. Richard D, Timofeeva E. Energy balance regulation: complex interplay between the autonomic and cognitive/limbic brains to control food intake and thermogenesis. In: Johnson C, editor. Obesity Prevention: The Role of Brain and Society on Individual Behavior. Oxford: Elsevier (2010). p. 299-316.
149. Parker JA, Bloom SR. Hypothalamic neuropeptides and the regulation of appetite. Neuropharmacology (2012) 63:18-30. doi:10.1016/j.neuropharm.2012.02.004.
150. Richard D, Timofeeva E. Energy homeostasis: paraventricular nucleus (PVN) system. In: Squire LR, editor. Encyclopedia of Neuroscience. Berlin: Elsevier (2009). p. 1035-41.
151. Barson JR, Morganstern I, Leibowitz SF. Complementary roles of orexin and melanin-concentrating hormone in feeding behaviour. Int J Endocrinol (2013) 2013:983964. doi:10.1155/2013/983964.
152. Elmquist JK, Elias CF, Saper CB. From lesions to leptin: hypothalamic control of food intake and body weight. Neuron (1999) 22:221-32. doi:10.1016/S0896-6273(00)81084-3.
153. Baskin DG, Figlewicz Lattemann D, Seeley RJ, Woods SC, Porte DJ, Schwartz MW. Insulin and leptin: dual adiposity signals to the brain for the regulation of food intake and body weight. Brain Res (1999) 848:114-23. doi:10.1016/S0006-8993(99)01974-5.
154. Varela L, Horvath TL. Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis. EMBO Rep (2012) 13:1079-86. doi:10.1038/embor.2012.174.
155. Kristensen P, Judge ME, Thim L, Ribel U, Christjansen KN, WulffBS, et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature (1998) 393:72-6. doi:10.1038/29993.
156. Williams KW, Margatho LO, Lee CE, Choi M, Lee S, Scott MM, et al. Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons. J Neurosci (2010) 30:2472-9. doi:10.1523/JNEUROSCI.3118-09.2010.
157. Wang Q, Liu C, Uchida A, Chuang JC, Walker A, Liu T, et al. Arcuate AgRP neurons mediate orexigenic and glucoregulatory action of ghrelin. Mol Metab (2014) 3:64-72. doi:10.1016/j.molmet.2013.10.001.
158. Disse E, Bussier AL, Veyrat-Durebex C, Deblon N, Pfluger PT, Tschöp MH, et al. Peripheral ghrelin enhances sweet taste food consumption and preference, regardless of its caloric content. Physiol Behav (2010) 101:277-81. doi:10.1016/j.physbeh.2010.05.017.
159. Olszewski PK, Klockars A, Olszewska AM, Fredriksson R, Schiöth HB, Levine AS. Molecular, immunohistochemical, and pharmacological evidence of oxytocin's role as inhibitor of carbohydrate but not fat intake. Endocrinology (2010) 151:4736-44. doi:10.1210/en.2010-0151.
160. Leibowitz SF, Akabayashi A, Alexander J, Karatayev O, Chang GQ. Puberty onset in female rats: relationship with fat intake, ovarian steroids and the peptides, galanin and enkephalin, in the paraventricular and medial preoptic nuclei. J Neuroendocrinol (2009) 21:538-49. doi:10.1111/j.1365-2826.2009.01870.x.
161. Mizushige T, Saitoh K, Manabe Y, Nishizuka T, Taka Y, Eguchi A, et al. Preference for dietary fat induced by release of beta-endorphin in rats. Life Sci (2009) 84:760-5. doi:10.1016/j.lfs.2009.03.003.
162. Ogawa N, Ito M, Yamaguchi H, Shiuchi T, Okamoto S, Wakitani K, et al. Intestinal fatty acid infusion modulates food preference as well as calorie intake via the vagal nerve and midbrain-hypothalamic neural pathways in rats. Metabolism (2012) 61:1312-20. doi:10.1016/j.metabol.2012.02.011.
163. Gardiner JV, Campbell D, Patterson M, Kent A, Ghatei MA, Bloom SR, et al. The hyperphagic effect of ghrelin is inhibited in mice by a diet high in fat. Gastroenterology (2010) 138:2468-76. doi:10.1053/j.gastro.2010.02.012.
164. Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, et al. Ketosis and appetite-mediating nutrients and hormones after weight loss. Eur J Clin Nutr (2013) 67:759-64. doi:10.1038/ejcn.2013.90.
165. Shen C, Yu T, Tang ZH, Wu KM. Changes in ghrelin and obestatin levels before and after a meal in children with simple obesity and anorexia. Horm Res Paediatr (2013) 79:341-6. doi:10.1159/000351464.
166. Singhal V, Misra M, Klibanski A. Endocrinology of anorexia nervosa in young people: recent insights. Curr Opin Endocrinol Diabetes Obes (2014) 21(1):64-70. doi:10.1097/MED.0000000000000026.
167. Guillory B, Splenser A, Garcia J. The role of ghrelin in anorexia-cachexia syndromes. Vitam Horm (2013) 92:61-106. doi:10.1016/B978-0-12-410473-0.00003-9.
168. Invernizzi M, Carda S, Cisari C. On behalf of Società Italiana per lo Studio della Sarcopenia e della Disabilità Muscolo-Scheletrica (SISDIM). Possible synergism of physical exercise and ghrelin-agonists in patients with cachexia associated with chronic heart failure. Aging Clin Exp Res (2014). doi:10.1007/s40520-013-0186-7.
169. Vezzani A, Sperk G. Overexpression of NPY and Y2 receptors in epileptic brain tissue: an endogenous neuroprotective mechanism in temporal lobe epilepsy? Neuropeptides (2004) 38:245-52. doi:10.1016/j.npep.2004.05.004.
170. Mazarati AM, Hohmann JG, Bacon A, Liu H, Sankar R, Steiner RA, et al. Modulation of hippocampal excitability and seizures by galanin. J Neurosci (2000) 20:6276-81.
171. Ataie Z, Golzar MG, Babri SH, Ebrahimi H, Mohaddes G. Does ghrelin level change after epileptic seizure in rats? Seizure (2011) 20:347-9. doi:10.1016/j.seizure.2011.01.001.
172. Aydin S, Dag E, Ozkan Y, Arslan O, Koc G, Bek S, et al. Time-dependent changes in the serum levels of prolactin, nesfatin-1 and ghrelin as a marker of epileptic attacks young male patients. Peptides (2011) 32:1276-80. doi:10.1016/j.peptides.2011.04.021.
173. Gall C. Seizures induce dramatic and distinctly different changes in enkephalin, dynorphin, and CCK immunoreactivities in mouse hippocampal mossy fibers. J Neurosci (1988) 8:1852-62.
174. Wyeth MS, Zhang N, Mody I, Houser CR. Selective reduction of cholecystokinin-positive basket cell innervation in a model of temporal lobe epilepsy. J Neurosci (2010) 30:8993-9006. doi:10.1523/JNEUROSCI.1183-10.2010.
175. Arslan G, Alici SK, Ayyildiz M, Agar E. The role of CB1-receptors in the proconvulsant effect of leptin on penicillin-induced epileptiform activity in rats. CNS Neurosci Ther (2013) 19:222-8. doi:10.1111/cns.12075.
176. Jeon BT, Shin HJ, Kim JB, Kim YK, Lee DH, Kim KH, et al. Adiponectin protects hippocampal neurons against kainic acid-induced excitotoxicity. Brain Res Rev (2009) 61:81-8. doi:10.1016/j.brainresrev.2009.05.002.
177. Lee EB, Warmann G, Dhir R, Ahima RS. Metabolic dysfunction associated with adiponectin deficiency enhances kainic acid-induced seizure severity. J Neurosci (2011) 31:14361-6. doi:10.1523/JNEUROSCI.3171-11.2011.
178. Ahima RS. Metabolic actions of adipocyte hormones: focus on adiponectin. Obesity (2006) 14(Suppl 1):9S-15S. doi:10.1038/oby.2006.276.
179. Nishimura M, Izumiya Y, Higuchi A, Shibata R, Qiu J, Kudo C, et al. Adiponectin prevents cerebral ischemic injury through endothelial nitric oxide synthase dependent mechanisms. Circulation (2008) 117:216-23. doi:10.1161/CIRCULATIONAHA.107.725044.
180. Chen B, Liao WQ, Xu N, Xu H, Wen JY, Yu CA, et al. Adiponectin protects against cerebral ischemia-reperfusion injury through anti-inflammatory action. Brain Res (2009) 1273:129-37. doi:10.1016/j.brainres.2009.04.002.
181. Obay BD, Tasdemir E, Tümer C, Bilgin HM, Sermet A. Antiepileptic effects of ghrelin on pentylenetetrazole-induced seizures in rats. Peptides (2007) 28:1214-9. doi:10.1016/j.peptides.2007.04.003.
182. Aslan A, Yildirim M, Ayyildiz M, Güven A, Agar E. The role of nitric oxide in the inhibitory effect of ghrelin against penicillin-induced epileptiform activity in rat. Neuropeptides (2009) 43:295-302. doi:10.1016/j.npep.2009.05.005.
183. Lee J, Lim E, Kim Y, Li E, Park S. Ghrelin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus. J Endocrinol (2010) 205:263-70. doi:10.1677/JOE-10-0040.
184. Biagini G, Torsello A, Marinelli C, Gualtieri F, Vezzali R, Coco S, et al. Beneficial effects of desacyl-ghrelin, hexarelin and EP-80317 in models of status epilepticus. Eur J Pharmacol (2011) 670:130-6. doi:10.1016/j.ejphar.2011.08.020.
185. Lucchi C, Curia G, Vinet J, Gualtieri F, Bresciani E, Locatelli V, et al. Protective but not anticonvulsant effects of ghrelin and JMV-1843 in the pilocarpine model of status epilepticus. PLoS One (2013) 8(8):e72716. doi:10.1371/journal.pone.0072716.
186. Biagini G, Locatelli V, Torsello A. Ghrelin anticonvulsive properties: is it a matter of desacylation? Epilepsia (2012) 53:1277-8. doi:10.1111/j.1528-1167.2012.03546.x.
187. Bulgarelli I, Tamiazzo L, Bresciani E, Rapetti D, Caporali S, Lattuada D, et al. Desacyl-ghrelin and synthetic GH-secretagogues modulate the production of inflammatory cytokines in mouse microglia cells stimulated by beta-amyloid fibrils. J Neurosci Res (2009) 87:2718-27. doi:10.1002/jnr.22088.
188. Xu L, Rensing N, Yang XF, Zhang HX, Thio LL, Rothman SM, et al. Leptin inhibits 4-aminopyridine-and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents. J Clin Invest (2008) 118:272-80. doi:10.1172/JCI33009.
189. Erbayat-Altay E, Yamada KA, Wong M, Thio LL. Increased severity of pentylenetetrazol induced seizures in leptin deficient ob/ob mice. Neurosci Lett (2008) 433:82-6. doi:10.1016/j.neulet.2007.12.051.
190. Aslan A, Yildirim M, Ayyildiz M, Güven A, Agar E. Interaction of leptin and nitric oxide pathway on penicillin-induced epileptiform activity in rats. Brain Res (2010) 1321:117-24. doi:10.1016/j.brainres.2010.01.054.
191. Lynch JJ III, Shek EW, Castagné V, Mittelstadt SW. The proconvulsant effects of leptin on glutamate receptor-mediated seizures in mice. Brain Res Bull (2010) 82:99-103. doi:10.1016/j.brainresbull.2010.02.003.
192. Noè F, Pool AH, Nissinen J, Gobbi M, Bland R, Rizzi M, et al. Neuropeptide Y gene therapy decreases chronic spontaneous seizures in a rat model of temporal lobe epilepsy. Brain (2008) 131:1506-15. doi:10.1093/brain/awn079.
193. Mazarati A, Wasterlain CG. Anticonvulsant effects of four neuropeptides in the rat hippocampus during self-sustaining status epilepticus. Neurosci Lett (2002) 331:123-7. doi:10.1016/S0304-3940(02)00847-9.
194. Baraban SC. Antiepileptic actions of neuropeptide Y in the mouse hippocampus require Y5 receptors. Epilepsia (2002) 43(Suppl 5):9-13. doi:10.1046/j.1528-1157.43.s.5.13.x.
195. Howell OW, Silva S, Scharfman HE, Sosunov AA, Zaben M, Shatya A, et al. Neuropeptide Y is important for basal and seizure-induced precursor cell proliferation in the hippocampus. Neurobiol Dis (2007) 26:174-88. doi:10.1016/j.nbd.2006.12.014.
196. Agasse F, Bernardino L, Kristiansen H, Christiansen SH, Ferreira R, Silva B, et al. Neuropeptide Y promotes neurogenesis in murine subventricular zone. Stem Cells (2008) 26:1636-45. doi:10.1634/stemcells.2008-0056.
197. Kovac S, Walker MC. Neuropeptides in epilepsy. Neuropeptides (2013) 47:467-75. doi:10.1016/j.npep.2013.10.015.
198. Greco R, Latini G, Chiarelli F, Iannetti P, Verrotti A. Leptin, ghrelin, and adiponectin in epileptic patients treated with valproic acid. Neurology (2005) 65:1808-9. doi:10.1212/01.wnl.0000187074.27586.d1.
199. Berilgen MS, Mungen B, Ustundag B, Demir C. Serum ghrelin levels are enhanced in patients with epilepsy. Seizure (2006) 15:106-11. doi:10.1016/j.seizure.2005.11.008.
200. Gungor S, Yücel G, Akinci A, Tabel Y, Ozerol IH, Yologlu S. The role of ghrelin in weight gain and growth in epileptic children using valproate. J Child Neurol (2007) 22:1384-8. doi:10.1177/0883073807307096.
201. Aydin S, Dag E, Ozkan Y, Erman F, Dagli AF, Kilic N, et al. Nesfatin-1 and ghrelin levels in serum and saliva of epileptic patients: hormonal changes can have a major effect on seizure disorders. Mol Cell Biochem (2009) 328:49-56. doi:10.1007/s11010-009-0073-x.
202. Prodam F, Bellone S, Casara G, De Rienzo F, Grassino EC, Bonsignori I, et al. Ghrelin levels are reduced in prepubertal epileptic children under treatment with carbamazepine or valproic acid. Epilepsia (2010) 51:312-5. doi:10.1111/j.1528-1167.2009.02307.x.
203. Curia G, Lucchi C, Vinet J, Gualtieri F, Marinelli C, Torsello A, et al. Pathophysiogenesis of mesial temporal lobe epilepsy: is prevention of damage antiepileptogenic? Curr Med Chem (2014) 21:663-88. doi:10.2174/0929867320666131119152201.
204. Cansu A, Serdaroglu A, Cinaz P. Serum insulin, cortisol, leptin, neuropeptide Y, galanin and ghrelin levels in epileptic children receiving oxcarbazepine. Eur J Paediatr Neurol (2011) 15:527-31. doi:10.1016/j.ejpn.2011.05.004.
205. Tokgoz H, Aydin K, Oran B, Kiyici A. Plasma leptin, neuropeptide Y, ghrelin, and adiponectin levels and carotid artery intima media thickness in epileptic children treated with valproate. Childs Nerv Syst (2012) 228:1049-53. doi:10.1007/s00381-012-1788-7.
206. Lancha A, Frühbeck G, Gómez-Ambrosi J. Peripheral signalling involved in energy homeostasis control. Nutr Res Rev (2012) 25:223-48. doi:10.1017/S0954422412000145.
207. Riediger T. The receptive function of hypothalamic and brainstem centres to hormonal and nutrient signals affecting energy balance. Proc Nutr Soc (2012) 71:463-77. doi:10.1017/S0029665112000778.
208. Williams KW, Elmquist JK. From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior. Nat Neurosci (2012) 15:1350-5. doi:10.1038/nn.3217.
209. Fraser DA, Thoen J, Bondhus S, Haugen M, Reseland JE, Djøseland O, et al. Reduction in serum leptin and IGF-1 but preserved T-lymphocyte numbers and activation after a ketogenic diet in rheumatoid arthritis patients. Clin Exp Rheumatol (2000) 18:209-14.
210. Rauchenzauner M, Klepper J, Leiendecker B, Luef G, Rostasy K, Ebenbichler C. The ketogenic diet in children with Glut1 deficiency syndrome and epilepsy. J Pediatr (2008) 153:716-8. doi:10.1016/j.jpeds.2008.05.012.
211. Kinzig KP, Hargrave SL, Hyun J, Moran TH. Energy balance and hypothalamic effects of a high-protein/low-carbohydrate diet. Physiol Behav (2007) 92:454-60. doi:10.1016/j.physbeh.2007.04.019.
212. Huda MS, Dovey TM, Wong SP, English PJ, Halford JC, McCulloch P, et al. Ghrelin does not orchestrate the metabolic changes seen in fasting but has significant effects on lipid mobilisation and substrate utilisation. Eur J Endocrinol (2011) 165:45-55. doi:10.1530/EJE-10-1122.
213. Veldhuis JD, Bowers CY. Integrating GHS into the ghrelin system. Int J Pept (2010) 2010: doi:10.1155/2010/879503.
214. Ogiso K, Asakawa A, Amitani H, Inui A. Ghrelin and anorexia nervosa: a psychosomatic perspective. Nutrition (2011) 27:988-93. doi:10.1016/j.nut.2011.05.005.
215. Vergnano AM, Ferrini F, Salio C, Lossi L, Baratta M, Merighi A. The gastrointestinal hormone ghrelin modulates inhibitory neurotransmission in deep laminae of mouse spinal cord dorsal horn. Endocrinology (2008) 149:2306-12. doi:10.1210/en.2007-1164.
216. Toshinai K, Yamaguchi H, Sun Y, Smith RG, Yamanaka A, Sakurai T, et al. Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Endocrinology (2006) 147:2306-14. doi:10.1210/en.2005-1357.
217. InhoffT, Wiedenmann B, Klapp BF, Mönnikes H, Kobelt P. Is desacyl ghrelin a modulator of food intake? Peptides (2009) 30:991-4. doi:10.1016/j.peptides.2009.01.019.
218. Chen CY, Inui A, Asakawa A, Fujino K, Kato I, Chen CC, et al. Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats. Gastroenterology (2005) 129:8-25. doi:10.1053/j.gastro.2005.04.015.
219. Iwakura H, Hosoda K, Son C, Fujikura J, Tomita T, Noguchi M, et al. Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagon promoter-ghrelin transgenic mice. J Biol Chem (2005) 280:15247-56. doi:10.1074/jbc. M411358200.
220. Guerlavais V, Boeglin D, Mousseaux D, Oiry C, Heitz A, Deghenghi R, et al. New active series of growth hormone secretagogues. J Med Chem (2003) 46:1191-203. doi:10.1021/jm020985q.
221. Moulin A, Demange L, Ryan J, Mousseaux D, Sanchez P, Bergé G, et al. New trisubstituted 1,2,4-triazole derivatives as potent ghrelin receptor antagonists. 3. Synthesis and pharmacological in vitro and in vivo evaluations. J Med Chem (2008) 51:689-93. doi:10.1021/jm701292s.
222. Demange L, Boeglin D, Moulin A, Mousseaux D, Ryan J, Bergé G, et al. Synthesis and pharmacological in vitro and in vivo evaluations of novel triazole derivatives as ligands of the ghrelin receptor. 1. J Med Chem (2007) 50:1939-57. doi:10.1021/jm070024h.
223. Demers A, McNicoll N, Febbraio M, Servant M, Marleau S, Silverstein R, et al. Identification of the growth hormone-releasing peptide binding site in CD36: a photoaffinity cross-linking study. Biochem J (2004) 382:417-24. doi:10.1042/BJ20040036.
224. Balosso S, Maroso M, Sanchez-Alavez M, Ravizza T, Frasca A, Bartfai T, et al. A novel non-transcriptional pathway mediates the proconvulsive effects of interleukin-1β. Brain (2008) 131:3256-65. doi:10.1093/brain/awn271.
225. Glezer I, Bittencourt JC, Rivest S. Neuronal expression of Cd36, Cd44, and Cd83 antigen transcripts maps to distinct and specific murine brain circuits. J Comp Neurol (2009) 517:906-24. doi:10.1002/cne.22185.