The role of leptin in the sporadic form of Alzheimer's disease. Interactions with the adipokines amylin, ghrelin and the pituitary hormone prolactin

Life Sciences

Volumn 140, Issue , 2015, Pages 19-28

  Folch, Jaume ^a,c   Patraca, Iván ^a,c   Martínez, Nohora ^a,c   Pedrós, Ignacio ^a,b   Petrov, Dmitry ^b,c   Ettcheto, Miren ^b,c   Abad, Sonia ^b,c   Marin, Miguel ^f   Beas Zarate, Carlos ^d,e   Camins, Antoni ^b,c,f  

^a FACULTAT DE MEDICINA I CIÈNCIES DE LA SALUT   (Spain)

^b UNIVERSITY OF BARCELONA   (Spain)

^c CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED SOBRE ENFERMEDADES NEURODEGENERATIVAS CIBERNED   (Spain)

^d UNIVERSITY OF GUADALAJARA   (Mexico)

^e INSTITUTO MEXICANO DEL SEGURO SOCIAL   (Mexico)

^f UNIVERSIDAD NACIONAL DE LOJA   (Ecuador)

Author keywords

Alzheimer's disease; Amylin; Ghrelin; High fat diet; Hippocampus; Insulin receptor; Leptin; mTOR; Obesity; PGC 1 ; Prolactin

Indexed keywords

AMYLIN; GHRELIN; LEPTIN; PROLACTIN; PROTEIN BINDING;

ALZHEIMER DISEASE; ARTICLE; BLOOD BRAIN BARRIER; BODY WEIGHT; FOOD INTAKE; HIPPOCAMPUS; HUMAN; HYPOTHALAMUS; INFLAMMATION; LIFESTYLE; LIPID DIET; LIPID HOMEOSTASIS; NERVOUS SYSTEM DEVELOPMENT; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; BLOOD; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY;

ALZHEIMER DISEASE; DIABETES MELLITUS, TYPE 2; GHRELIN; HUMANS; HYPOTHALAMUS; ISLET AMYLOID POLYPEPTIDE; LEPTIN; LIFE STYLE; OBESITY; PROLACTIN; PROTEIN BINDING;

EID: 84944441668     PISSN: 00243205     EISSN: 18790631     Source Type: Journal    
DOI: 10.1016/j.lfs.2015.05.002     Document Type: Review

References (132)

1. H. Hampel, D. Prvulovic, S. Teipel, F. Jessen, C. Luckhaus, L. Frolich, M.W. Riepe, R. Dodel, T. Leyhe, L. Bertram, W. Hoffmann, and F. Faltraco German Task Force on Alzheimer's Disease. The future of Alzheimer's disease: the next 10 years Prog. Neurobiol. 95 2011 718 728 10.1016/j.pneurobio.2011.11.008
2. A. Wimo, L. Jonsson, J. Bond, M. Prince, B. Winblad, and Alzheimer Disease International The worldwide economic impact of dementia 2010 Alzheimer's Dement, J. Alzheimer's Assoc 9 2013 1 11 10.1016/j.jalz.2012.11.006
3. C. Qiu, and L. Fratiglioni Epidemiology of dementia P. McNamara, Dementia Treatments and Developments 2011 ABC-CLIO California 1 33
4. C. Reitz, C. Brayne, and R. Mayeux Epidemiology of Alzheimer disease Nat. Rev. Neurol. 7 2011 137 152 10.1038/nrneurol.2011.2
5. A. Erol An integrated and unifying hypothesis for the metabolic basis of sporadic Alzheimer's disease J. Alzheimers Dis. 13 2008 241 253
6. S.W. Pimplikar Reassessing the amyloid cascade hypothesis of Alzheimer's disease Int. J. Biochem. Cell Biol. 41 2009 1261 1268 10.1016/j.biocel.2008.12.015
7. C. Ballard, S. Gauthier, A. Corbett, C. Brayne, D. Aarsland, and E. Jones Alzheimer's disease Lancet 377 2011 1019 1031 10.1016/S0140-6736(10)61349-9
8. R.J. Castellani, R.K. Rolston, and M.A. Smith Alzheimer disease Dis. Mon. 56 2010 484 546
9. J.A. Hardy, and G.A. Higgins Alzheimer's disease: the amyloid cascade hypothesis Science 256 1992 184 185 10.1126/science.1566067
10. J.A. Hardy, and D.J. Selkoe The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics Science 297 2002 353 356 10.1126/science.1072994
11. N. Sato, and R. Morishita Plasma β-amyloid: a possible missing link between Alzheimer disease and diabetes Diabetes 62 2013 1005 1006 10.2337/db12-1549
12. W. Zhang, M. Bai, Y. Xi, and J. Hao Multiple inflammatory pathways are involved in the development and progression of cognitive deficits in APPswe/PS1dE9 mice Neurobiol. Aging 33 2012 2661 2677 10.1016/j.neurobiolaging.2011.12.023
13. M. Garcia-Alloza, E.M. Robbins, S.X. Zhang-Nunes, and S.M. Purcell Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease Neurobiol. Dis. 24 2009 516 524 10.1016/j.nbd.2006.08.017
14. Y. Urano, S. Ochiai, and N. Noguchi Suppression of amyloid-β production by 24S-hydroxycholesterol via inhibition of intracellular amyloid precursor protein trafficking FASEB J. 27 2013 4305 4315 10.1096/fj.13-231456
15. B. Reed, S. Villeneuve, W. Mack, C. Decarli, H.C. Chui, and W. Jagust Associations between serum cholesterol levels and cerebral amyloidosis JAMA Neurol 71 2014 195 200
16. E. Barbero-Camps, A. Fernández, L. Martínez, J.C. Fernández-Checa, and A. Colell APP/PS1 mice overexpressing SREBP-2 exhibit combined Aβ accumulation and tau pathology underlying Alzheimer's disease Hum. Mol. Genet. 22 2013 3460 3476 10.1093/hmg/ddt201
17. A.S. Buchman, R.S. Wilson, J.L. Bienias, R.C. Shah, D.A. Evans, and D.A. Bennett Change in body mass index and risk of incident Alzheimer disease Neurology 65 2005 892 897 10.1212/01.wnl.0000176061.33817.90
18. L. Haataja, T. Gurlo, C.J. Huang, and P.C. Butler Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis Endocr. Rev. 29 2008 303 316 10.1210/er.2007-0037
19. M. Hiltunen, V.K. Khandelwal, N. Yaluri, T. Tiilikainen, M. Tusa, H. Koivisto, M. Krzisch, S. Vepsäläinen, P. Mäkinen, S. Kemppainen, P. Miettinen, A. Haapasalo, H. Soininen, M. Laakso, and H. Tanila Contribution of genetic and dietary insulin resistance to Alzheimer phenotype in APP/PS1 transgenic mice J. Cell. Mol. Med. 16 2012 1206 1222 10.1111/j.1582-4934.2011.01384.x
20. S. Koga, A. Kojima, S. Kuwabara, and Y. Yoshiyama Immunohistochemical analysis of tau phosphorylation and astroglial activation with enhanced leptin receptor expression in diet-induced obesity mouse hippocampus Neurosci. Lett. 571 2014 11 16 10.1016/j.neulet.2014.04.028
21. I.A. Arnoldussen, A.J. Kiliaan, and D.R. Gustafson Obesity and dementia: adipokines interact with the brain Eur. Neuropsychopharmacol. 24 2014 1982 1999 10.1016/j.euroneuro.2014.03.002
22. J.L. Sobesky, R.M. Barrientos, H.S. De May, B.M. Thompson, M.D. Weber, L.R. Watkins, and S.F. Maier High-fat diet consumption disrupts memory and primes elevations in hippocampal IL-1β, an effect that can be prevented with dietary reversal or IL-1 receptor antagonism Brain Behav. Immun. 42 2014 22 32 10.1016/j.bbi.2014.06.017
23. K.S. Sellbom, and J. Gunstad Cognitive function and decline in obesity J. Alzheimers Dis. 30 Suppl. 2 2012 S89 S95
24. S.E. Kanoski, and T.L. Davidson Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity Physiol. Behav. 103 2011 59 68 10.1016/j.physbeh.2010.12.003
25. G. Winocur, and C.E. Greenwood Studies of the effects of high fat diets on cognitive function in a rat model Neurobiol. Aging 26 Suppl. 1 2005 46 49 10.1016/j.neurobiolaging.2005.09.003
26. I. Valladolid-Acebes, P. Stucchi, V. Cano, M.S. Fernandez-Alfonso, B. Merino, M. Gil-Ortega, A.A. Fole, L. Morales, M. Ruiz-Gayo, and N. Del Olmo High-fat diets impair spatial learning in the radial-arm maze in mice Neurobiol. Learn. Mem. 95 2011 80 85 10.1016/j.nlm.2010.11.007
27. S. Kosari, E. Badoer, J.C. Nguyen, A.S. Killcross, and T.A. Jenkins Effect of western and high fat diets on memory and cholinergic measures in the rat Behav. Brain Res. 235 2012 98 103 10.1016/j.bbr.2012.07.017
28. A.P. Ross, E.C. Bruggeman, A.W. Kasumu, J.G. Mielke, and M.B. Parent Nonalcoholic fatty liver disease impairs hippocampal-dependent memory in male rats Physiol. Behav. 106 2012 133 141 10.1016/j.physbeh.2012.01.008
29. N. Yamada-Goto, G. Katsuura, Y. Ochi, K. Ebihara, T. Kusakabe, K. Hosoda, and K. Nakao Impairment of fear-conditioning responses and changes of brain neurotrophic factors in diet-induced obese mice J. Neuroendocrinol. 24 2012 1120 1125 10.1111/j.1365-2826.2012.02327.x
30. S. Hoyer Glucose metabolism and insulin receptor signal transduction in Alzheimer disease Eur. J. Pharmacol. 490 2004 115 125 10.1016/j.ejphar.2004.02.049
31. S. Merlo, S. Spampinato, P.L. Canonico, A. Copani, and M.A. Sortino Alzheimer's disease: brain expression of a metabolic disorder? Trends Endocrinol. Metab. 21 2010 537 544 10.1016/j.tem.2010.05.005
32. V. Frisardi, V. Solfrizzi, D. Seripa, C. Capurso, A. Santamato, D. Sancarlo, G. Vendemiale, A. Pilotto, and F. Panza Metabolic-cognitive syndrome: a cross-talk between metabolic syndrome and Alzheimer's disease Ageing Res. Rev. 9 2010 399 417 10.1016/j.arr.2010.04.007
33. M. Hokama, S. Oka, J. Leon, T. Ninomiya, H. Honda, K. Sasaki, T. Iwaki, T. Ohara, T. Sasaki, F.M. Laferla, Y. Kiyohara, and Y. Nakabeppu Altered expression of diabetes-related genes in Alzheimer's disease brains: the Hisayama Study Cereb. Cortex 24 2014 2476 2488 10.1093/cercor/bht101
34. L.D. Baker, D. Cross, S. Minoshima, D. Belongia, G. Stennis, and S. Watson Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes Arch. Neurol. 68 2011 51 57 10.1001/archneurol.2010.225
35. R.C. Frederich, A. Hamann, S. Anderson, B. Löllmann, B.B. Lowell, and J.S. Flier Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action Nat. Med. 1 1995 1311 1314 10.1038/nm1295-1311
36. K.C. de Git, R.A. Adan, Leptin resistance in diet-induced obesity: the role of hypothalamic inflammation, Obes. Rev., 2015, http://dx.doi.org/10.1111/obr.12243
37. L. Zhou, C. Yuan, J. Zhang, R. Yu, M. Huang, I.M. Adcock, and X. Yao Circulating leptin concentrations in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis Respiration 86 2013 512 522 10.1159/000354191
38. G.H. Ballantyne, A. Gumbs, and I.M. Modlin Changes in insulin resistance following bariatric surgery and the adipoinsular axis: role of the adipocytokines, leptin, adiponectin and resistin Obes. Surg. 15 2005 692 699 10.1381/0960892053923789
39. T.J. Kieffer, and J.F. Habener The adipoinsular axis: effects of leptin on pancreatic beta-cells Am. J. Physiol. Endocrinol. Metab. 278 2000 E1 E14
40. J.C. Henquin, and H.P. Meissner Opposite effects of tolbutamide and diazoxide on 86Rb + fluxes and membrane potential in pancreatic B cells Biochem. Pharmacol. 31 1982 1407 1415 10.1016/0006-2952(82)90036-3
41. R. Alemzadeh, and K.M. Tushaus Modulation of adipoinsular axis in prediabetic zucker diabetic fatty rats by diazoxide Endocrinology 145 2004 5476 5484 10.1210/en.2003-1523
42. Y. Zhang, R. Proenca, M. Maffei, M. Barone, L. Leopold, and J.M. Friedman Positional cloning of the mouse obese gene and its human homologue Nature 372 1994 425 432 10.1038/372425a0
43. L. Gautron, and J.K. Elmquist Sixteen years and counting: an update on leptin in energy balance J. Clin. Invest. 121 2011 2087 2093 10.1172/JCI45888
44. S. Koga, A. Kojima, C. Ishikawa, S. Kuwabara, K. Arai, and Y. Yoshiyama Effects of diet-induced obesity and voluntary exercise in a tauopathy mouse model: implications of persistent hyperleptinemia and enhanced astrocytic leptin receptor expression Neurobiol. Dis. 71 2014 180 192 10.1016/j.nbd.2014.08.015
45. J.M. Zigman, and J.K. Elmquist Minireview: from anorexia to obesity - the yin and yang of body weight control Endocrinology 144 2003 3749 3756
46. S.H. Bates, W.H. Stearns, T.A. Dundon, M. Schubert, A.W. Tso, Y. Wang, A.S. Banks, H.J. Lavery, A.K. Haq, E. Maratos-Flier, B.G. Neel, M.W. Schwartz Jr., and M.G. Myers STAT3 signalling is required for leptin regulation of energy balance but not reproduction Nature 421 2003 856 859 10.1038/nature01388
47. G. Ramadori, T. Fujikawa, M. Fukuda, J. Anderson, D.A. Morgan, R. Mostoslavsky, R.C. Stuart, M. Perello, C.R. Vianna, E.A. Nillni, K. Rahmouni, and R. Coppari SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity Cell Metab. 12 2010 78 87 10.1016/j.cmet.2010.05.010
48. G. Ramadori, C.E. Lee, A.L. Bookout, S. Lee, K.W. Williams, J. Anderson, J.K. Elmquist, and R. Coppari Brain SIRT1: anatomical distribution and regulation by energy availability J. Neurosci. 28 2008 9989 9996 10.1523/JNEUROSCI.3257-08.2008
49. M. Ishii, G. Wang, G. Racchumi, J.P. Dyke, and C. Iadecola Transgenic mice overexpressing amyloid precursor protein exhibit early metabolic deficits and a pathologically low leptin state associated with hypothalamic dysfunction in arcuate neuropeptide Y neurons J. Neurosci. 34 2014 9096 9106 10.1523/JNEUROSCI.0872-14.2014
50. J.P. Thaler, S.J. Choi, M.W. Schwartz, and B.E. Wisse Hypothalamic inflammation and energy homeostasis: resolving the paradox Front. Neuroendocrinol. 31 2010 79 84 10.1016/j.yfrne.2009.10.002
51. W. Fu, A. Ruangkittisakul, D. MacTavish, J.Y. Shi, K. Ballanyi, and J.H. Jhamandas Amyloid β (Aβ) peptide directly activates amylin-3 receptor subtype by triggering multiple intracellular signaling pathways J. Biol. Chem. 287 2012 18820 18830 10.1074/jbc.M111.331181
52. S. Söderberg, B. Ahrén, M. Eliasson, and B. Dinesen T. Olsson T. The association between leptin and proinsulin is lost with central obesity J. Intern. Med. 252 2002 140 148 10.1046/j.1365-2796.2002.01018.x
53. E. Hartter, T. Svoboda, B. Ludvik, M. Schuller, B. Lell, E. Kuenburg, M. Brunnbauer, W. Woloszczuk, R. Prager. Basal and stimulated plasma levelsof pancreatic amylin indicate itsco-secretion with insulin in humans, Diabetologia, 34 (1991) 52-54. http://dx.doi.org/10.1007/BF00404025
54. J.E. Koda, M. Fineman, T.J. Rink, G.E. Dailey, D.B. Muchmore, and L.G. Linarelli Amylin concentrations and glucose control Lancet 339 1992 1179 1180 10.1016/0140-6736(92)90785-2
55. A.A. Young, B. Gedulin, W. Vine, A. Percy, and T.J. Rink Gastric emptying is accelerated in diabetic BB rats and is slowed by subcutaneous injections of amylin Diabetologia 38 1995 642 648 10.1007/BF00401833
56. T. Riediger, M. Rauch, and H. Schmid Actions of amylin on subfornical organ neurons and on drinking behaviour in rats Am. J. Physiol. 276 1999 R514 R521
57. P.C. May, L.N. Boggs, and K.S. Fuson Neurotoxicity of human amylin in rat primary hippocampal cultures: similarity to Alzheimer's disease amyloid-beta neurotoxicity J. Neurochem. 61 1993 2330 2333 10.1111/j.1471-4159.1993.tb07480.x
58. J.E. Morley, J.F. Flood, S.A. Farr, H.J. Perry, F.E. Kaiser, and P.E. Morley Effects of amylin on appetite regulation and memory Can. J. Physiol. Pharmacol. 73 1995 1042 1046 10.1139/y95-147
59. C. De Vriese, and C. Delporte Influence of ghrelin on food intake and energy homeostasis Curr. Opin. Clin. Nutr. Metab. Care 10 2007 615 659 10.1097/MCO.0b013e32829fb37c
60. M.D. Gahete, A. Rubio, J. Córdoba-Chacón, F. Gracia-Navarro, R.D. Kineman, J. Avila, R.M. Luque, and J.P. Casta-o Expression of the ghrelin and neurotensin systems is altered in the temporal lobe of Alzheimer's disease patients J. Alzheimers Dis. 22 2010 819 828
61. X.M. Guan, H. Yu, O.C. Palyha, K.K. McKee, S.D. Feighner, D.J. Sirinathsinghji, R.G. Smith, L.H. Van der Ploeg, and A.D.J. Howard Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues Brain Res. Mol. Brain Res. 48 1997 23 29 10.1016/S0169-328X(97)00071-5
62. M. Nakazato, N. Murakami, Y. Date, M. Kojima, H. Matsuo, K. Kangawa, and S. Matsukura A role for ghrelin in the central regulation of feeding Nature 409 2001 194 198 10.1038/35051587
63. V.P. Carlini, M.E. Monzon, M.M. Varas, A.B. Cragnolini, H.B. Schioth, T.N. Scimonelli, and S.R. Barioglio Ghrelin increases anxiety-like behavior and memory retention in rats Biochem Biophys Res Commun 299 2002 739 743 10.1016/S0006-291X(02)02740-7
64. H. Cai, W.N. Cong, J.I. WN, S. Ji, S. Rothman, S. Maudsley, and B. Martin Metabolic dysfunction in Alzheimer's disease and related neurodegenerative disorders Curr. Alzheimer Res. 9 2012 5 17 10.2174/156720512799015064
65. Z. Cai, L.J. Yan, K. Li, S.H. Quazi, and B. Zhao Roles of AMP-activated protein kinase in Alzheimer's disease Neuromolecular Med. 14 2012 1 14 10.1007/s12017-012-8173-2
66. M. Moon, J.G. Choi, D.W. Nam, H.S. Hong, Y.J. Choi, M.S. Oh, and I. Mook-Jung Ghrelin ameliorates cognitive dysfunction and neurodegeneration in intrahippocampal amyloid-b1-42 oligomer-injected mice J. Alzheimers Dis. 23 2011 147 159
67. Y. Chen, C.P. Cao, C.R. Li, W. Wang, D. Zhang, L.L. Han, X.Q. Zhang, A. Kim, S. Kim, and G.L. Liu Ghrelin modulates insulin sensitivity and tau phosphorylation in high glucose-induced hippocampal neurons Biol. Pharm. Bull. 33 2010 1165 1169 10.1248/bpb.33.1165
68. V. Giordano, G. Peluso, M. Iannuccelli, P. Benatti, and M. Calvani Systemic and brain metabolic dysfunction as a new paradigm for approaching Alzheimer's dementia Neurochem. Res. 32 2007 555 567 10.1007/s11064-006-9125-8
69. W.N. Cong, E. Golden, N. Pantaleo, C.M. White, S. Maudsley, and B. Martin Ghrelin receptor signaling: a promising therapeutic target for metabolic syndrome and cognitive dysfunction CNS Neurol. Disord. Drug Targets 9 2010 557 563 10.2174/187152710793361513
70. S. Gomes, I. Martins, A.C. Fonseca, C.R. Oliveira, R. Resende, and C.M. Pereira Protective effect of leptin and ghrelin against toxicity induced by amyloid-β oligomers in a hypothalamic cell line J. Neuroendocrinol. 26 2014 176 185 10.1111/jne.12138
71. E.C. McNay, and A.K. Recknagel Brain insulin signaling: a key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes Neurobiol. Learn. Mem. 96 2011 432 442 10.1016/j.nlm.2011.08.005
72. G. Marwarha, and O. Ghribi Leptin signaling and Alzheimer's disease Am J Neurodegener Dis 1 2012 245 265
73. S.J. Greco, K.J. Bryan, S. Sarkar, X. Zhu, M.A. Smith, J.W. Ashford, J.M. Johnston, N. Tezapsidis, and G. Casadesus Leptin reduces pathology and improves memory in a transgenic mouse model of Alzheimer's disease J. Alzheimers Dis. 19 2010 1155 1167
74. S.J. Greco, A. Hamzelou, J.M. Johnston, M.A. Smith, J.W. Ashford, and N. Tezapsidis Leptin boosts cellular metabolism by activating AMPK and the sirtuins to reduce tau phosphorylation and β-amyloid in neurons Biochem. Biophys. Res. Commun. 14 2011 170 174 10.1016/j.bbrc.2011.09.050
75. G. McGregor, Y. Malekizadeh, and J. Harvey Minireview: food for thought: regulation of synaptic function by metabolic hormones Mol. Endocrinol. 29 2015 3 13 10.1210/me.2014-1328
76. G. Marwarha, S. Raza, C. Meiers, and O. Ghribi Leptin attenuates BACE1 expression and amyloid-β genesis via the activation of SIRT1 signaling pathway Biochim. Biophys. Acta 1842 2014 1587 1595 10.1016/j.bbadis.2014.05.015
77. A.J. Irving, and J. Harvey Leptin regulation of hippocampal synaptic function in health and disease Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 369 2013 2013 2055 10.1098/rstb.2013.0155
78. J.M. Johnston, W.T. Hu, D.W. Fardo, S.J. Greco, G. Perry, T.J. Montine, J.Q. Trojanowski, L.M. Shaw, J.W. Ashford, and N. Tezapsidis Low plasma leptin in cognitively impaired ADNI subjects: gender differences and diagnostic and therapeutic potential Curr. Alzheimer Res. 1 2 2014 165 174
79. J.M. Johnston, S.J. Greco, A. Hamzelou, J.W. Ashford, and N. Tezapsidis Repositioning leptin as a therapy for Alzheimer's disease Therapy 8 5 2011 481 490
80. J. Folch, I. Pedrós, I. Patraca, F. Sureda, F. Junyent, C. Beas-Zarate, E. Verdaguer, M. Pallàs, C. Auladell, and A. Camins Neuroprotective and anti-ageing role of leptin J. Mol. Endocrinol. 49 2012 R149 R156 10.1530/JME-12-0151
81. I. Pedrós, D. Petrov, M. Allgaier, F. Sureda, E. Barroso, C. Beas-Zarate, C. Auladell, M. Pallàs, M. Vázquez-Carrera, G. Casadesús, J. Folch, and A. Camins Early alterations in energy metabolism in the hippocampus of APPswe/PS1dE9 mouse model of Alzheimer's disease Biochim. Biophys. Acta 1842 2014 1556 1566 10.1016/j.bbadis.2014.05.025
82. M.E. Orr, A. Salinas, R.A. Buffenstein, and S. Oddo Mammalian target of rapamycin hyperactivity mediates the detrimental effects of a high sucrose diet on Alzheimer's disease pathology Neurobiol. Aging 35 2014 1233 1242 10.1016/j.neurobiolaging.2013.12.006
83. K. Hegyi, K. Fülöp, K. Kovács, S. Tóth, and A. Falus Leptin-induced signal transduction pathways Cell Biol. Int. 28 2004 159 169 10.1016/j.cellbi.2003.12.003
84. M. Mannaa, S. Kramer, M. Boschmann, and M. Gollasch mTOR and regulation of energy homeostasis in humans J. Mol. Med. 91 2013 1167 1175
85. Z. Tang, E. Bereczki, H. Zhang, S. Wang, C. Li, X. Ji, R.M. Branca, J. Lehtiö, Z. Guan, P. Filipcik, S. Xu, B. Winblad, and J.J. Pei Mammalian target of rapamycin (mTor) mediates tau protein dyshomeostasis: implication for Alzheimer disease J. Biol. Chem. 31 288 2013 15556 155570
86. S. Wullschleger, R. Loewith, and M.N. Hall TOR signaling in growth and metabolism Cell 124 2006 471 484 10.1016/j.cell.2006.01.016
87. A.K. Saha, X.J. Xu, T.W. Balon, A. Brandon, E.W. Kraegen, and N.B. Ruderman Insulin resistance due to nutrient excess: is it a consequence of AMPK downregulation? Cell Cycle 10 2011 3447 3451 10.4161/cc.10.20.17886
88. N.A. Shirwany, M.H. Zou, AMPK: a cellular metabolic and redox sensor. A minireview, Front Biosci (Landmark Ed), 19 (2014) 447-474. 10.2741/4218
89. L. Katsouri, C. Parr, N. Bogdanovic, M. Willem, and M. Sastre PPARγ co-activator-1α (PGC-1α) reduces amyloid-β generation through a PPARγ-dependent mechanism J. Alzheimers Dis. 25 2011 151 162
90. A. Louis, A. Bartke, and M.M. Masternak Effects of growth hormone and thyroxine replacement therapy on insulin signaling in Ames dwarf mice J. Gerontol. A Biol. Sci. Med. Sci. 65 2010 344 352 10.1093/gerona/glq018
91. N. Laflamme, and S. Rivest Toll-like receptor 4: the missing link of the cerebral innate immune response triggered by circulating gram-negative bacterial cell wall components FASEB J. 15 2001 155 163 10.1096/fj.00-0339com
92. S.S. Martin, A. Qasim, and M.P. Reilly Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease J. Am. Coll. Cardiol. 52 2008 1201 1210 10.1016/j.jacc.2008.05.060
93. S. Maioli, M. Lodeiro, P. Merino-Serrais, F. Falahati, W. Khan, E. Puerta, A. Codita, R. Rimondini, M.J. Ramirez, A. Simmons, F. Gil-Bea, E. Westman, and A. Cedazo-Minguez The Alzheimer's disease neuroimaging initiative. Alterations in brain leptin signalling in spite of unchanged CSF leptin levels in Alzheimer's disease Aging Cell 14 2015 122 129 10.1111/acel.12281
94. H. Hsuchou, W. Pan, M.J. Barnes, and A.J. Kastin Leptin receptor mRNA in rat brain astrocytes Peptides 30 2009 2275 2280 10.1016/j.peptides.2009.08.023
95. G. Munch, J. Apelt, J. Rosemarie, E. Kientsch, P. Stahl, H.J. Luth, and R. Schliebs Advanced glycation endproducts and pro-inflammatory cytokines in transgènic Tg2576 mice with amyloid plaque pathology J. Neurochem. 86 2003 283 289 10.1046/j.1471-4159.2003.01837.x
96. Y. Zhu, E. Nwabuisi-Heath, S.B. Dumanis, L.M. Tai, C. Yu, G.W. Rebeck, and M.J. LaDu APOE genotype alters glial activation and loss of synaptic markers in mice Glia 60 2012 559 569 10.1002/glia.22289
97. E. Fuente-Martín, C. García-Cáceres, M. Granado, M.L. de Ceballos, M.A. Sánchez-Garrido, B. Sarman, Z.W. Liu, M.O. Dietrich, M. Tena-Sempere, P. Argente-Arizón, F. Díaz, J. Argente, T.L. Horvath, and J.A. Chowen Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes J. Clin. Invest. 122 2012 3900 3913 10.1172/JCI64102
98. B.T. Jeon, E.A. Jeong, H.J. Shin, Y. Lee, D.H. Lee, H.J. Kim, S.S. Kang, G.J. Cho, W.S. Choi, and G.S. Roh Resveratrol attenuates obesity-associated peripheral and central inflammation and improves memory deficit in mice fed a high-fat diet Diabetes 61 2012 1444 1454 10.2337/db11-1498
99. P. Agostinho, R.A. Cunha, and C. Oliveira Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer's Disease Curr. Pharm. Des. 16 2010 2766 2778 10.2174/138161210793176572
100. D. Farfara, V. Lifshitz, and D. Frenkel Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease J. Cell. Mol. Med. 12 2008 762 780 10.1111/j.1582-4934.2008.00314.x
101. G. Azizi, and A. Mirshafiey The potential role of proinflammatory and antiinflammatory cytokines in Alzheimer disease pathogenesis Immunopharmacol. Immunotoxicol. 34 2012 881 895 10.3109/08923973.2012.705292
102. C.T. De Souza, E.P. Araujo, S. Bordin, R. Ashimine, R.L. Zollner, A.C. Boschero, M.J. Saad, and L.A. Velloso Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus Endocrinology 146 10 2005 4192 4199 10.1210/en.2004-1520
103. M. Milanski, G. Degasperi, A. Coope, J. Morari, R. Denis, D.E. Cintra, D.M. Tsukumo, G. Anhe, M.E. Amaral, H.K. Takahashi, R. Curi, H.C. Oliveira, J.B. Carvalheira, S. Bordin, M.J. Saad, and L.A. Velloso Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity J. Neurosci. 29 2009 359 370 10.1523/JNEUROSCI.2760-08.2009
104. J. Lee, E. Lim, Y. Kim, E. Li, and S. Park Ghrelin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus J. Endocrinol. 205 2010 263 270 10.1677/JOE-10-0040
105. M.G. De Simoni, C. Perego, T. Ravizza, D. Moneta, M. Conti, F. Marchesi, A. De Luigi, S. Garattini, and A. Vezzani Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus Eur. J. Neurosci. 12 2000 2623 2633 10.1046/j.1460-9568.2000.00140.x
106. T. Ravizza, M. Rizzi, C. Perego, C. Richichi, J. Velísková, S.L. Moshé, M.G. De Simoni, and A. Vezzani Inflammatory response and glia activation in developing rat hippocampus after status epilepticus Epilepsia 46 2005 113 117 10.1111/j.1528-1167.2005.01006.x
107. E. Erbayat-Altay, A.J. Fessler, M. Gallagher, H.P. Attarian, F. Dehdashti, V.J. Vahle, J. Ojemann, J.L. Dowling, and F.G. Gilliam Correlation of severity of FDG-PET hypometabolism and interictal regional delta slowing in temporal lobe epilepsy Epilepsia 46 2005 573 576 10.1111/j.0013-9580.2005.08204.x
108. G. Biagini, A. Torsello, C. Marinelli, F. Gualtieri, R. Vezzali, S. Coco, E. Bresciani, and V. Locatelli Beneficial effects of desacyl-ghrelin, hexarelin and EP-80317 in models of status epilepticus Eur. J. Pharmacol. 670 2011 130 136 10.1016/j.ejphar.2011.08.020
109. M.W. Warren, L.S. Hynan, and M.F. Weiner Lipids and adipokines as risk factors for Alzheimer's disease J. Alzheimers Dis. 29 2012 151 157
110. M.E. Freeman, S. Kanyicska, and A. Lerant Prolactin: structure, function, and regulation of secretion Physiol. Rev. 80 2000 1523 1631
111. V. Popovic, and L.H. Duntas Brain somatic cross-talk: ghrelin, leptin and ultimate challengers of obesity Nutr. Neurosci. 8 2005 1 5 10.1080/10284150400027107
112. D. Tejadilla, M. Cerbón, and T. Morales Prolactin reduces the damaging effects of excitotoxicity in the dorsal hippocampus of the female rat independently of ovarian hormones Neuroscience 169 2010 1178 1185 10.1016/j.neuroscience.2010.05.074
113. C.J. Phelps, M.I. Romero, and D.L. Hurley Prolactin replacement must be continuous and initiated prior to 21 d of age to maintain hypothalamic dopaminergic neurons in hypopituitary mice Endocrine 20 2003 139 148 10.1385/ENDO:20:1-2:139
114. M. Furuta, and R.S. Bridges Gestation-induced cell proliferation in the rat brain Brain Res. Dev. Brain Res. 156 2005 61 66 10.1016/j.devbrainres.2005.01.008
115. D. Mangoura, C. Pelletiere, S. Leung, N. Sakellaridis, and D.X. Wang Prolactin concurrently activates src-PLD and JAK/Stat signaling pathways to induce proliferation while promoting differentiation in embryonic astrocytes Int. J. Dev. Neurosci. 18 2000 693 704 10.1016/S0736-5748(00)00031-9
116. L. Torner, S. Karg, A. Blume, M. Kandasamy, H.G. Kuhn, J. Winkler, L. Aigner, and I.D. Neumann Prolactin prevents chronic stress-induced decrease of adult hippocampal neurogenesis and promotes neuronal fate J. Neurosci. 29 2009 1826-1833 10.1523/JNEUROSCI.3178-08.2009
117. V. Goffin, N. Binart, P. Touraine, and P.A. Kelly Prolactin: the new biology of an old hormone Annu Ver Physiol 64 2002 47 67 10.1146/annurev.physiol.64.081501.131049
118. T. Morales Recent findings on neuroprotection against excitotoxicity in the hippocampus of female rats J. Neuroendocrinol. 23 2011 994 1001 10.1111/j.1365-2826.2011.02141.x
119. C.K. Tipsmark, C.N. Strom, S.T. Bailey, and R.J. Borski Leptin stimulates pituitary prolactin release through an extracellular signal-regulated kinase-dependent pathway J. Endocrinol. 196 2008 275 281 10.1677/JOE-07-0540
120. V.S. Nagaishi, L. Cardinali, T.T. Zampieri, I.C. Furigo, M. Metzger, and J. Donato Jr. Possible crosstalk between leptin and prolactin during pregnancy Neuroscience 259 2014 71 83 10.1016/j.neuroscience.2013.11.050
121. R.A. Augustine, and D.R. Grattan Induction of central leptin resistance in hyperphagic pseudopregnant rats by chronic prolactin infusion Endocrinology 149 2008 1049 1055 10.1210/en.2007-1018
122. S.R. Ladyman, R.A. Augustine, and D.R. Grattan Hormone interactions regulating energy balance during pregnancy J. Neuroendocrinol. 22 2010 805 817 10.1111/j.1365-2826.2010.02017.x
123. A.M. De Paoli 20 years of leptin: leptin in common obesity and associated disorders of metabolism J. Endocrinol. 223 2014 71 81 10.1530/JOE-14-0258
124. J.D. Roth, B.L. Roland, R.L. Cole, J.L. Trevaskis, C. Weyer, J.E. Koda, C.M. Anderson, D.G. Parkes, and A.D. Baron Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies Proc. Natl. Acad. Sci. U. S. A. 105 2008 7257 7262 10.1073/pnas.0706473105
125. J.L. Trevaskis, V.F. Turek, C. Wittmer, P.S. Griffin, J.K. Wilson, J.M. Reynolds, Y. Zhao, C.M. Mack, D.G. Parkes, and J.D. Roth Enhanced amylin-mediated body weight loss in estradiol-deficient diet-induced obese rats Endocrinology 151 2010 5657 5668 10.1210/en.2010-0590
126. V.F. Turek, J.L. Trevaskis, B.E. Levin, A.A. Dunn-Meynell, B. Irani, G. Gu, C. Wittmer, P.S. Griffin, C. Vu, D.G. Parkes, and J.D. Roth Mechanisms of amylin/leptin synergy in rodent models Endocrinology 151 2010 143 152 10.1210/en.2009-0546
127. C. Le Foll, M.D. Johnson, A. Dunn-Meynell, C.N. Boyle, T.A. Lutz, and B.E. Levin Amylin-induced central IL-6 production enhances ventromedial hypothalamicleptin signalling Diabetes 2014 Nov 19 pii: DB-140645
128. S. Jager, C. Handschin, J. St-Pierre, and S.M. Spiegelman AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha Proc. Natl. Acad. Sci. U. S. A. 104 2007 12017 12022 10.1073/pnas.0705070104
129. F.Y. Ma, G.M. Anderson, T.D. Gunn, V. Goffin, D.R. Grattan, and S.J. Bunn Prolactin specifically activates signal transducer and activator of transcription 5b in neuroendocrine dopaminergic neurons Endocrinology 146 2005 5112 5119 10.1210/en.2005-0770
130. J.A. Ríos, P. Cisternas, M. Arrese, S. Barja, and N.C. Inestrosa Is Alzheimer's disease related to metabolic syndrome? A Wnt signaling conundrum Prog. Neurobiol. 121 2014 125 146 10.1016/j.pneurobio.2014.07.004
131. M. Sadowski, J. Pankiewicz, H. Scholtzova, Y. Ji, D. Quartermain, and C.H. Jensen Amyloid-beta deposition is associated with decreased hippocampal glucose metabolism and spatial memory J. Neuropathol. Exp. Neurol. 63 2004 418 428
132. M.W. Schwartz, and G.J. Morton Obesity: keeping hunger at bay Nature 418 2002 595 597 10.1038/418595a