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Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease

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Abstract

Increasing evidence suggests that regular consumption of coffee, tea and dark chocolate (cacao) can promote brain health and may reduce the risk of age-related neurodegenerative disorders. However, the complex array of phytochemicals in coffee and cacao beans and tea leaves has hindered a clear understanding of the component(s) that affect neuronal plasticity and resilience. One class of phytochemicals present in relatively high amounts in coffee, tea and cacao are methylxanthines. Among such methylxanthines, caffeine has been the most widely studied and has clear effects on neuronal network activity, promotes sustained cognitive performance and can protect neurons against dysfunction and death in animal models of stroke, Alzheimer’s disease and Parkinson’s disease. Caffeine’s mechanism of action relies on antagonism of various subclasses of adenosine receptors. Downstream xanthine metabolites, such as theobromine and theophylline, may also contribute to the beneficial effects of coffee, tea and cacao on brain health.

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References

  1. Fredholm BB, Battig K, Holmen J, Nehlig A, Zxartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133

    CAS  PubMed  Google Scholar 

  2. Trivino AH (2013) Chocolate: the story of Nahuatlism. Estudios de Cultura Nahuatl 46:37–87

    Google Scholar 

  3. Dicum G, Luttinger N (1999) The coffee book: anatomy of an industry from crop to the last drop. The New Press, New York

    Google Scholar 

  4. Kunz H (2002) Emil Fischer – unequalled classicist, master of organic chemistry research, and inspired trailblazer of biological chemistry. Agnew Chem Int Ed 41:4439–4451

    Article  CAS  Google Scholar 

  5. Donovan JL, DeVane CL (2001) A primer on caffeine pharmacology and its drug interactions in clinical psychopharmacology. Psychopharmacol Bull 35:30–48

    CAS  PubMed  Google Scholar 

  6. Mattson MP (2015) What doesn’t kill you…. Sci Am 313:40–45

    Article  PubMed  PubMed Central  Google Scholar 

  7. Stidworthy MF, Bleakley JS, Cheeseman MT, Kelly DF (1997) Chocolate poisoning in dogs. Vet Rec 141:28

    CAS  PubMed  Google Scholar 

  8. Nathanson JA (1984) Caffeine and related methylxanthines: possible naturally occurring pesticides. Science 226:184–187

    Article  CAS  PubMed  Google Scholar 

  9. Lee J, Jo DG, Park D, Chung HY, Mattson MP (2014) Adaptive cellular stress pathways as therapeutic targets of dietary phytochemicals: focus on the nervous system. Pharmacol Rev 66:815–868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Johnson-Kozlow M, Kritz-Silverstein D, Barrett-Connor E, Morton D (2002) Coffee consumption and cognitive function among older adults. Am J Epidemiol 156:842–850

    Article  PubMed  Google Scholar 

  11. Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M (2009) Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. J Alzheimers Dis 16:85–91

    Article  CAS  PubMed  Google Scholar 

  12. Powers KM, Kay DM, Factor SA, Zabetian CP, Higgins DS, Samii A, Nutt JG, Griffith A, Leis B, Roberts JW, Martinez ED, Montimurro JS, Checkoway H, Payami H (2008) Combined effects of smoking, coffee, and NSAIDs on Parkinson’s disease risk. Mov Disord 23:88–95

    Article  PubMed  Google Scholar 

  13. Ma QP, Huang C, Cui QY, Yang DJ, Sun K, Chen X, Li XH (2016) Meta-Analysis of the Association between Tea Intake and the Risk of Cognitive Disorders. PLoS One 11:e0165861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Blanchard J, Sawers SJ (1983) The absolute bioavailability of caffeine in man. Eur J Clin Pharmacol 24:93–98

    Article  CAS  PubMed  Google Scholar 

  15. Chvasta TE, Cooke AR (1971) Emptying and absorption of caffeine from the human stomach. Gastroenterology 61:838–843

    Article  CAS  PubMed  Google Scholar 

  16. Tang-Liu DD, Williams RL, Reigelman S (1983) Disposition of caffeine and its metabolites in man. J Pharmacol Exp Ther 224:180–185

    CAS  PubMed  Google Scholar 

  17. Arnaud MJ (1993) Metabolism of caffeine and other components of coffee. In: Garattini S (ed) Caffeine, coffee and health. Raven, New York, pp 43–95

    Google Scholar 

  18. Arnaud MJ (2011) Pharmocokinetics and metabolism of natural methyxanthines in animal and man. In: Fredholm BB (ed) Handbook of experimental pharmacology, vol 200. Springer, Berlin, pp 33–92

    Google Scholar 

  19. Kalow W, Tang BK (1993) The use of caffeine for enzyme assays: a critical appraisal. Clin Pharmacol Ther 53:503–514

    Article  CAS  PubMed  Google Scholar 

  20. Gu L, Gonzalez FJ, Kalow W, Tang BK (1992) Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics 2:73–77

    Article  CAS  PubMed  Google Scholar 

  21. Benowitz NL, Jacob P 3rd, Mayan H, Denaro C (1995) Sympathomimetic effects of paraxanthine and caffeine in humans. Clin Pharmacol Ther 58:684–691

    Article  CAS  PubMed  Google Scholar 

  22. Tang-Liu DD, Riegelman S (1981) Metabolism of theophylline to caffeine in adults. Res Commun Chem Pathol Pharmacol 34:371–380

    CAS  PubMed  Google Scholar 

  23. Gates S, Miners JO (1999) Cytochrome P450 isoform selectivity in human hepatic theobromine metabolism. Br J Clin Pharmacol 47:299–305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lelo A, Birkett DJ, Miners JO (1990) Mechanism of formation of 6-amino-5-(N-methylformylamino)-1-methyluracil and 3,7-dimethyluric acid from theobromine in the rat in vitro: involvementof cytochrome P-450 and a cellular thiol. Xenobiotica 20:823–833

    Article  CAS  PubMed  Google Scholar 

  25. International Agency for Research on Cancer (1991) International Agency for Research on Cancer (IARC) monographs on the evaluation of carcinogenic risks to humans: coffee, tea, mate, methylxanthines and methylglyoxal. WHO, Geneva

    Google Scholar 

  26. Lelo A, Birkett DJ, Robson RA, Miners JO (1986) Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man. Br J Clin Pharmacol 22:177–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Arnaud MJ (1976) Identification, kinetic and quantitative study of [2-14C] and [1-Me-14C] caffeine metabolites in rat’s urine by chromatographic separations. Biochem Med 16:67–76

    Article  CAS  PubMed  Google Scholar 

  28. Wilkinson JM, Pollard I (1993) Accumulation of theophylline, theobromine and paraxanthine in the fetal rat brain following a single oral dose of caffeine. Brain Res Dev Brain Res 75:193–199

    Article  CAS  PubMed  Google Scholar 

  29. Stahle L (1991) Drug distribution studies with microdialysis: I. Tissue dependent difference in recovery between caffeine and theophylline. Life Sci 49:1835–1842

    Article  CAS  PubMed  Google Scholar 

  30. Yoneda M, Sugimoto N, Katakura M, Matsuzaki K, Tanigami H, Yachie A, Onho-Shosaku T, Shido O (2017) Theobromine up-regulates cerebral brain-derived neurotrophic factor and facilitates motor learning in mice. J Nutr Biochem 39:110–116

    Article  CAS  PubMed  Google Scholar 

  31. Arnaud MJ, Enslen M (1992) The role of paraxanthine in mediating physiological effects of caffeine. In: 14th international conference in coffee science, San Francisco, 14–19. Proceedings ASIC, Paris, pp 71–79

  32. Arnold ME, Petros TV, Beckwith BE, Coons G, Gorman N (1987) The effects of caffeine, impulsivity, and sex on memory for word lists. Physiol Behav 41:25–30

    Article  CAS  PubMed  Google Scholar 

  33. Hameleers PA, Van Boxtel MP, Hogervorst E, Riedel WJ, Houx PJ, Buntinx F, Jolles J (2000) Habitual caffeine consumption and its relation to memory, attention, planning capacity and psychomotor performance across multiple age groups. Hum Psychopharmacol 15:573–581

    Article  PubMed  Google Scholar 

  34. Kelemen WL, Creeley CE (2003) State-dependent memory effects using caffeine and placebo do not extend to metamemory. J Gen Psychol 130:70–86

    Article  PubMed  Google Scholar 

  35. Smit HJ, Gaffan EA, Rogers PJ (2004) Methylxanthines are the psycho-pharmacologically active constituents of chocolate. Psychopharmacology 176:412–419

    Article  CAS  PubMed  Google Scholar 

  36. Mitchell ES, Slettenaar M, vd Meer N, Transler C, Jans L, Quadt F, Berry M (2011) Differential contributions of theobromine and caffeine on mood, psychomotor performance and blood pressure. Physiol Behav 104:816–822

    Article  CAS  PubMed  Google Scholar 

  37. Scholey A, Owen L (2013) Effects of chocolate on cognitive function and mood: a systematic review. Nutr Rev 71:665–681

    Article  PubMed  Google Scholar 

  38. Ritchie K, Carrière I, de Mendonca A, Portet F, Dartigues JF, Rouaud O, Barberger-Gateau P, Ancelin ML (2007) The neuroprotective effects of caffeine: a prospective population study (the Three City Study). Neurology 69:536–545

    Article  CAS  PubMed  Google Scholar 

  39. Corley J, Jia X, Kyle JA, Gow AJ, Brett CE, Starr JM, McNeill G, Deary IJ (2010) Caffeine consumption and cognitive function at age 70: the Lothian Birth Cohort 1936 study. Psychosom Med 72:206–214

    Article  PubMed  Google Scholar 

  40. Institute of Medicine (2001) Caffeine for the sustainment of mental task performance: formulations for military operations. Washington, DC: National Academy Press

    Google Scholar 

  41. van Boxtel MP, Schmitt JA, Bosma H, Jolles J (2003) The effects of habitual caffeine use on cognitive change: a longitudinal perspective. Pharmacol Biochem Behav 75:921–927

    Article  CAS  PubMed  Google Scholar 

  42. van Gelder BM, Buijsse B, Tijhuis M, Kalmijn S, Giampaoli S, Nissinen A, Kromhout D (2007) Coffee consumption is inversely associated with cognitive decline in elderly European men: the FINE study. Eur J Clin Nutr 61:226–232

    Article  PubMed  Google Scholar 

  43. Desideri G, Kwik-Uribe C, Grassi D, Necozione S, Ghiadoni L, Mastroiacovo D, Raffaele A, Ferri L, Bocale R, Lechiara MC, Marini C, Ferri C (2012) Benefits in cognitive function, blood pressure, and insulin resistance through cocoa flavanol consumption in elderly subjects with mild cognitive impairment: The cocoa, cognition, and aging (CoCoA) study. Hypertension 60:794–801

    Article  CAS  PubMed  Google Scholar 

  44. Mastroiacovo D, Kwik-Uribe C, Grassi D, Necozione S, Raffaele A, Pistacchio L, Righetti R, Bocale R, Lechiara MC, Marini C, Ferri C, Desideri G (2015) Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: the cocoa, cognition, and aging (CoCoA) study–a randomized controlled trial. Am J Clin Nutr 101:538–548

    Article  CAS  PubMed  Google Scholar 

  45. Stavric B, Gilbert SG (1990) Caffeine metabolism: a problem in extrapolating results from animal studies to humans. Acta Parm Jugosl 40:475–489

    CAS  Google Scholar 

  46. Beavo JA, Rogers NL, Crofford OB, Hardman JG, Sutherland EW, Newman EV (1970) Effects of xanthine derivatives on lipolysis and on adenosine 3′,5′-monophosphate phosphodiesterase activity. Mol Pharmacol 6:597–603

    CAS  PubMed  Google Scholar 

  47. Francis SH, Sekhar KR, Ke H, Corbin JD (2011) Inhibition of cyclic nucleotide phosphodiesterase by methylxanthines and related compounds. In: Fredholm BB (ed) Handbook of experimental pharmacology. Springer, Berlin, pp 93–134

    Google Scholar 

  48. Rousseau E, Ladine J, Liu QY, Meissner G (1988) Activation of the Ca2 + release channel of skeletal muscle sarcoplasmic reticulum by caffeine and related compounds. Arch Biochem Biophys 267:75–86

    Article  CAS  PubMed  Google Scholar 

  49. Liu W, Meissner G (1997) Structure-activity relationship of xanthines and skeletal muscle ryanodine receptor/Ca2 + release channel. Pharmacology 54:135–143

    Article  CAS  PubMed  Google Scholar 

  50. Hawke TJ, Allen DG, Lindinger MI (2000) Paraxanthine, a caffeine metabolite, dose dependently increases [Ca(2+)](i) in skeletal muscle. J Appl Physiol 89:2312–2317

    Article  CAS  PubMed  Google Scholar 

  51. Pessah IN, Stambuk RA, Casida JE (1987) Ca2+-activated ryanodine binding: mechanisms of sensitivity and intensity modulation by Mg2+, caffeine, and adenine nucleotides. Mol Pharmacol 31:232–238

    CAS  PubMed  Google Scholar 

  52. Guerreiro S, Toulorge D, Hirsch E, Marien M, Sokoloff P, Michel PP (2008) Paraxanthine, the primary metabolite of caffeine, provides protection against dopaminergic cell death via stimulation of ryanodine receptor channels. Mol Pharmacol 74:980–989

    Article  CAS  PubMed  Google Scholar 

  53. Butcher RW, Sutherland EW (1962) Adenosine 3′,5′-phosphate in biological materials. I. Purification and properties of cyclic 3′,5′-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3′,5′-phosphate in human urine. J Biol Chem 237:1244–1250

    CAS  PubMed  Google Scholar 

  54. Fredholm BB (1985) On the mechanism of action of theophylline and caffeine. Acta Med Scand 217:149–153

    Article  CAS  PubMed  Google Scholar 

  55. Snyder SH, Katims JJ, Annau Z, Bruns RF, Daly JW (1981) Adenosine receptors and behavioral actions of methylxanthines. Proc Natl Acad Sci USA 78:3260–3264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Fredholm BB, Chen JF, Cunha RA, Svenningsson P, Vaugeois JM (2005) Adenosine and brain function. Int Rev Neurobiol 63:191–270

    Article  CAS  PubMed  Google Scholar 

  57. De Mendonca A, Ribeiro J (1996) Adenosine and neuronal plasticity. Life Sci 60:245–251

    Article  Google Scholar 

  58. Costenla AR, de Mendonca A, Ribeiro JA (1999) Adenosine modulates synaptic plasticity in hippocampal slices from aged rats. Brain Res 851:228–234

    Article  CAS  PubMed  Google Scholar 

  59. Yacoubi ME, Ledent C, Ménard JF, Parmentier M, Costentin J, Vaugeois JM (2000) The stimulant effects of caffeine on locomotor behaviour in mice are mediated through its blockade of adenosine A2A receptors. Br J Pharmacol 129:1465–1473

    Article  PubMed  PubMed Central  Google Scholar 

  60. De Mendonca A, Ribeiro JA (2001) Adenosine and synaptic plasticity. Drug Dev Res 52:283–290

    Article  Google Scholar 

  61. Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24:31–55

    Article  CAS  PubMed  Google Scholar 

  62. Costenla AR, Cunha RA, Mendonca A (2010) Caffeine, adenosine receptors, and synaptic plasticity. J Alzheimers Dis 20:S25-S34

    Article  CAS  Google Scholar 

  63. Reichert CF, Maire M, Schmidt C, Cajochen C (2016) Sleep-wake regulation and its impact on working memory performance: the role of adenosine. Biology 5:1–25 (Basel)

    Article  CAS  Google Scholar 

  64. Cunha RA (2005) Neuroprotection by adenosine in the brain: from A1 receptor activation to A2A receptor blockade. Purinergic Signal 1:111–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Daly JW (2007) Caffeine analogs: biomedical impact. Cell Mol Life Sci 64:2153–2169

    Article  CAS  PubMed  Google Scholar 

  66. Yang JN, Chen JF, Fredholm BB (2009) Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine. Am J Physiol Heart Circ Physiol 296:H1141–H1149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Cunha RA (2016) How does adenosine control neuronal dysfunction and neurodegeneration? J Neurochem 139:1019–1055

    Article  CAS  PubMed  Google Scholar 

  68. Ochiishi T, Saitoh Y, Yukawa A, Saji M, Ren Y, Shirao T, Miyamoto H, Nakata H, Sekino Y (1999) High level of adenosine A1 receptor-like immunoreactivity in the CA2/CA3a region of the adult rat hippocampus. Neuroscience 93:955–967

    Article  CAS  PubMed  Google Scholar 

  69. Arai A, Lynch G (1992) Factors regulating the magnitude of long-term potentiation induced by u pattern stimulation. Brain Res 598:173–184

    Article  CAS  PubMed  Google Scholar 

  70. Zhao M, Choi YS, Obrietan K, Dudek SM (2007) Synaptic plasticity (and the lack thereof) in hippocampal CA2 neurons. J Neurosci 27:12025–12032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Lee SE, Simons SB, Heldt SA, Zhao M, Schroeder JP, Vellano CP, Cowan DP, Ramineni S, Yates CK, Feng Y, Smith Y, Sweatt JD, Weinshenker D, Ressler KJ, Dudek SM, Hepler JR (2010) RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory. Proc Natl Acad Sci USA 107:16994–16998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Simons SB, Escobedo Y, Yasuda R, Dudek SM (2009) Regional differences in hippocampal calcium handling provide a cellular mechanism for limiting plasticity. Proc Natl Acad Sci USA 106:14080–14084

    Article  PubMed  PubMed Central  Google Scholar 

  73. Simons SB, Caruana DA, Zhao M, Dudek SM (2012) Caffeine-induced synaptic potential in hippocampal CA2 neurons. Nat Neurosci 15:23–25

    Article  CAS  Google Scholar 

  74. Costenla AR, Diógenes MJ, Canas PM, Rodrigues RJ, Nogueira C, Maroco J, Agostinho PM, Ribeiro JA, Cunha RA, de Mendonça A (2011) Enhanced role of adenosine A(2A) receptors in the modulation of LTP in the rat hippocampus upon ageing. Eur J Neurosci 34:12–21

    Article  PubMed  Google Scholar 

  75. Rebola N, Canas PM, Oliveira CR, Cunha RA (2005) Different synaptic and subsynaptic localization of adenosine A2A receptors in the hippocampus and striatum of the rat. Neroscience 132:893–903

    Article  CAS  Google Scholar 

  76. Lupica CR, Cass WA, Zahniser NR, Dunwiddie TV (1990) Effects of the selective adenosine A2 receptor agonist CGS 21680 on in vitro electrophysiology, cAMP formation and dopamine release in rat hippocampus and striatum. J Pharmacol Exp Ther 252:1134–1141

    CAS  PubMed  Google Scholar 

  77. Cunha RA, Constantino MD, Ribeiro JA (1997) ZM241385 is an antagonist of the facilitatory responses produced by the A2A adenosine receptor agonists CGS21680 and HENECA in the rat hippocampus. Br J Pharmacol 122:1279–1284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Rebola N, Lujan R, Cunha RA, Mulle C (2008) Adenosine A2A receptors are essential for long-term potentiation of NMDA-EPSCs at hippocampal mossy fiber synapses. Neuron 57:121–134

    Article  CAS  PubMed  Google Scholar 

  79. Li P, Rial D, Canas PM, Yoo JH, Li W, Zhou X, Wang Y, van Westen GJ, Payen MP, Augusto E, Goncalves N, Tome AR, Li Z, Wu Z, Zhou Y, IJzerman A, Boyden ES, Cunha RA, Qu J, Chen JF (2015) Optogenetic activation of intracellular adenosine A2A receptor signaling in the hippocampus is sufficient to trigger CREB phosphorylation and impair memory. Mol Psychiatry 20:1339–1349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Viana da Silva S, Habert MG, Zhang P, Bethge P, Lemos C, Goncalves N, Gorlewicz A, Malezieux M, Goncalves FQ, Grosjean N, Blanchet C, Frick A, Nagert UV, Cunha RA Mulle C (2016) Early synaptic deficits in the APP/PS1 mouse model of Alzheimer’s disease involve neuronal adenosine A2A receptors. Nat Commun 7:11915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Pagnussat N, Almeida AS, Marques DM, Nunes F, Chenet GC, Botton PH, Mioranza S, Loss CM, Cunha RA, Porciuncula LO (2015) Adenosine A(2A) receptors are necessary and sufficient to trigger memory impairment in adult mice. Br J Pharmacol 172:3831–3845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zhou SJ, Zhu ME, Shu D, Du XP, Song XH, Wang XT, Zheng RY, Cai XH, Chen JF, He JC (2009) Preferential enhancement of working memory in mice lacking adenosine A(2A) receptors. Brain Res 1303:74–83

    Article  CAS  PubMed  Google Scholar 

  83. Wei CJ, Singer P, Coelho J, Boison D, Feldon J, Yee BK, Chen JF (2011) Selective inactivation of adenosine A(2A) receptors in striatal neurons enhances working memory and reversal learning. Learn Mem 18:459–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Wei CJ, Augusto E, Gomes CA, Singer P, Wang Y, Boison D, Cunha RA, Yee BK, Chen JF (2014) Regulation of fear responses by striatal and extrastriatal adenosine A2A receptors in forebrain. Biol Psychiatry 75:855–863

    Article  CAS  PubMed  Google Scholar 

  85. Simoes AP, Machado NJ, Goncalves N, Kaster MP, Simoes AT, Nunes A, Pereira de Almeida L, Goosens KA, Rial D, Cunha RA (2016) Adenosine A2A receptors in the amygdala control synaptic plasticity and contextual fear memory. Neuropsychopharmacology 41:2862–2871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Prediger RD, Batista LC, Takahashi RN (2005) Caffeine reverses age-related deficits in olfactory discrimination and social recognition memory in rats. Involvement of adenosine A1 and A2A receptors. Neurobiol Aging 26:957–964

    Article  CAS  PubMed  Google Scholar 

  87. Kadowaki Horita T, Kobayashi M, Mori A, Jenner P, Kanda T (2013) Effects of the adenosine A2A antagonist istradefylline on cognitive performance in rats with a 6-OHDA lesion in prefrontal cortex. Psychopharmacol 230:345–352

    Article  CAS  Google Scholar 

  88. Dall’Igna OP, Fett P, Gomes MW, Souza DO, Cunha RA, Lara DR (2007) Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25–35)-induced cognitive deficits in mice. Exp Neurol 203:241–245

    Article  CAS  PubMed  Google Scholar 

  89. Cunha GM, Canas PM, Melo CS, Hockemeyer J, Müller CE, Oliveira CR, Cunha RA (2008) Adenosine A2A receptor blockade prevents memory dysfunction caused by beta-amyloid peptides but not by scopolamine or MK-801. Exp Neurol 210:776–781

    Article  CAS  PubMed  Google Scholar 

  90. Canas PM, Porciúncula LO, Cunha GM, Silva CG, Machado NJ, Oliveira JM, Oliveira CR, Cunha RA (2009) Adenosine A2A receptor blockade prevents synaptotoxicity and memory dysfunction caused by beta-amyloid peptides via p38 mitogen-activated protein kinase pathway. J Neurosci 29:14741–14751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Batalha VL, Pego JM, Fontinha BM, Costenla AR, Valadas JS, Baqi Y, Radjainia H, Muller CE, Sebastiao AM, Lopes LV (2013) Adenosine A2a receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation. Mol Psychiatry 18:320–331

    Article  CAS  PubMed  Google Scholar 

  92. Kaster MP, Machado NJ, Silva HB, Nunes A, Ardais AP, Santana M, Baqi Y, Muller CE, Rodrigues AL, Porciuncula LO, Chen JF, Tome AR, Agostinho P, Canas PM, Cinha AR (2015) Caffeine acts through neuronal adenosine A2A receptors to prevent mood memory disfunction triggered by chronic stress. Proc Natl Acad Sci USA 112:7833–7838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Albasanz JL, Perez S, Barrachina M, Ferrer I, Martin M (2008) Up-regulation of adenosine receptors in the frontal cortex in Alzheimer’s disease. Brain Pathol 18:211–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Orr AG, Hsiao EC, Wang MM, Ho K, Kim DH, Wang X, Guo W, Kang J, Yu GQ, Adame A, Devidze N, Dubal DB, Masliah E, Conkin BR, Mucke L (2015) Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory. Nat Neurosci 18:423–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Rebola N, Porciumcula LO, Lopes LV, Oliveira CR, Soares da Silva P, Cunha RA (2005) Long term effect of convulsive behavior on the density of adenosine A1 and A2A receptors in the rat cerebral cortex. Epilepsia 46:159–165

    Article  CAS  PubMed  Google Scholar 

  96. Nehlig A, Lucignani G, Kadekaro M, Porrino LJ, Sokoloff L (1984) Effects of acute administration of caffeine on local cerebral glucose utilization in the rat. Eur J Pharmacol 101:91–100

    Article  CAS  PubMed  Google Scholar 

  97. Nehlig A, Daval JL, Boyet S, Vert P (1986) Comparative effects of acute and chronic administration of caffeine on local cerebral glucose utilization in the conscious rat. Eur J Pharmacol 129:93–103

    Article  CAS  PubMed  Google Scholar 

  98. Nehlig A, Daval JL, Debry G (1992) Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic, and psychostimulant effects. Brain Res Brain Res Rev 17:139–170

    Article  CAS  PubMed  Google Scholar 

  99. Wright GA, Baker DD, Palmer MJ, Stabler D, Mustard JA, Power EF, Borland AM, Stevenson PC (2013) Caffeine in floral nectar enhances a pollinator’s memory of reward. Science 339:1202–1204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Strachecka A, Krauze M, Olszewski K, Borsuk G, Paleolog J, Merska M, Chobotow J, Bajda M, Grzyniwicz K (2014) Unexpected strong effect of caffeine on the vitality of western honeybees (Apis mellifera) Biochemistry 79:1192–1201

    CAS  PubMed  Google Scholar 

  101. Londos C, Cooper DM, Wolf J (1980) Subclasses of external adenosine receptors. Proc Natl Acad Scie USA 77:2551–2554

    Article  CAS  Google Scholar 

  102. van Calker D, Muller M, Hamprecht B (1979) Adenosine regulates via two types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem 33:999–1005

    Article  PubMed  Google Scholar 

  103. Fredholm BB, Chen Y, Franco R, Sitkovsky M (2007) Aspects of the general biology of adenosine A2A signaling. Prog Neurobiol 83:263–276

    Article  CAS  PubMed  Google Scholar 

  104. Dunwiddie TV, Hoffer BJ, Fredholm BB (1981) Alkylxanthines elevate hippocampal excitability. Evidence for a role of endogenous adenosine. Naunyn Schmiedebergs Arch Pharmacol 316:326–330

    Article  CAS  PubMed  Google Scholar 

  105. Kirsch GE, Codina J, Birnbaumer L, Brown AM (1990) Coupling of ATP-sensitive K + channels to A1receptors by G proteins in rat ventricular myocytes. Am J Physiol 259:H820-826

    Google Scholar 

  106. Scanziani M, Capogna M, Gahwiler BH, Thompson SM (1992) Presynaptic inhibition of miniature excitatory synaptic currents by baclofen and adenosine in the hippocampus. Neuron 9:919–927

    Article  CAS  PubMed  Google Scholar 

  107. Chen JF (2014) Adenosine receptor control of cognition in normal and disease. Int Rev Neurobiol 119:257–307

    Article  PubMed  Google Scholar 

  108. Faure M, Voyno-Yasenetskaya TA, Bourne HR (1994) cAMP and beta gamma subunits of heterotrimeric G proteins stimulate the mitogen-activated protein kinase pathway in COS-7 cells. J Biol Chem 269:7851–7854

    CAS  PubMed  Google Scholar 

  109. Gimenez-Llort L, Masino SA, Diao L, Fernandez-Teruel A, Tobena A, Halldner L et al (2005) Mice lacking the adenosine A(1) receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly. Synapse 57:8–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Kukley M, Schwan M, Fredholm BB, Dietrich D (2005) The role of extracellular adenosine in regulating mossy fiber synaptic plasticity. J Neurosci 25:2832–2837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Moore KA, Nicoll RA, Schmitz D (2003) Adenosine gates synaptic plasticity at hippocampal mossy fiber synapses. Proc Natl Acad Scie USA 100:14397–14402

    Article  CAS  Google Scholar 

  112. Florian C, Vecsey CG, Halassa MM, Haydon PG, Abel T (2011) Astrocyte-derived adenosine and A1 receptor activity contribute to sleep loss-induced deficits in hippocampal synaptic plasticity and memory in mice. J Neurosci 31:6956–6962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Lu G, Zhou QX, Kang S, Li QL, Zhai LC, Chen JD et al (2010) Chronic morphine treatment impaired hippocampal long-term potentiation and spatial memory via accumulation of extracellular adenosine acting on adenosine a1 receptors. J Neurosci 30:5058–5070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Gimenez-Llort L, Fernandez-Teruel A, Escorihuela RM, Fredholm BB, Tobena A, Pekny M et al (2002) Mice lacking the adenosine A1 receptor are anxious and aggressive, but are normal learners with reduced muscle strength and survival rate. Eur J Neurosci 16:547–550

    Article  PubMed  Google Scholar 

  115. Lang UE, Lang F, Ricther K, Vallon V, Lipp HP, Schermann J et al (2003) Emotional instability but intact spatial cognition in adenosine receptor knock out mice. Behav Brain Res 145:179–188

    Article  CAS  PubMed  Google Scholar 

  116. Hooper N, Fraser C, Stone TW (1996) Effects of purine analogues on spontaneous alterations in mice. Psycopharmacology 123:250–257

    Article  CAS  Google Scholar 

  117. Kull B, Svenningsson P, Fredholm BB (2000) Adenosine A2A receptors are co-localized with and activate Golf in rat striatum. Mol Pharmacol 58:771–777

    Article  CAS  PubMed  Google Scholar 

  118. Frank DA, Greenberg ME (1994) CREB: a mediator of long-term memory from mollusks to mammals. Cell 79:5–8

    Article  CAS  PubMed  Google Scholar 

  119. Tully T, Bourtchouladze R, Scott R, Tallman J (2003) Targeting the CREB pathway for memory enhancers. Nat Rev Drug Discov 2:267–277

    Article  CAS  PubMed  Google Scholar 

  120. Kandel ER (2012) The molecular biology of memory; cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Mol Brain 5:14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Gubitz AK, Widdowson L, Kurokawa M, Kirkpatrick KA, Richardson PJ (1996) Dual signaling by the adenosine A2A receptor involves activation of both N- and P-type calcium channels by different G proteins and protein kinases in the same striatal nerve terminals. J Neurochem 67:374–381

    Article  CAS  PubMed  Google Scholar 

  122. Cunha RA, Ribeiro JA (2000) ATP as a presynaptic modulator. Life Sci 68:119–137

    Article  CAS  PubMed  Google Scholar 

  123. Cunha RA, Ribeiro JA (2000) Purinergic modulation of [3H] GABA release from rat hippocampal nerve terminals. Neuropharmacol 39:1156–1167

    Article  CAS  Google Scholar 

  124. Vidi PA, Chemel BR, Hu CD, Watts VJ (2008) Ligand-dependent oligomerization of dopamine D(2) and adenosine A(2A) receptors in living neuronal cells. Mol Pharmacol 74:544–551

    Article  CAS  PubMed  Google Scholar 

  125. Ciruela F, Casado V, Rodrigues RJ, Lujan R, Burgueno J, Canals M, Borycz J, Rebola N, Goldberg SR, Mallol J, Cortes A, Canela EI, Lopez-Gimenez JF, Milligan G, Lluis C, Cunha RA, Ferre S, Franco R (2006) Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. J Neurosci 26:2080–2087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Hillion J, Canals M, Torvinen M, Casado V, Scott R, Terasmaa A, Hansson A, Watson S, Olah ME, Mallol J, Canela EI, Zoli M, Agnati LF, Ibanez CF, Lluis C, Franco R, Ferre S, Fuxe K (2002) Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem 277:18091–18097

    Article  CAS  PubMed  Google Scholar 

  127. Torvinen M, Marcellino D, Canals M, Agnati LF, Lluis C, Franco R, Fuxe K (2005) Adenosine A2A receptor and dopamine D3 receptor interactions: evidence of functional A2A/D3 heteromeric complexes. Mol Pharmacol 67:400–407

    Article  CAS  PubMed  Google Scholar 

  128. Diaz-Cabiale Z, Vivo M, Del Arco A, O’Connor WT, Harte MK, Muller CE, Martinez E, Popoli P, Fuxe K, Ferre S (2002) Metabotropic glutamate mGlu5 receptor-mediated modulation of the ventral striopallidal GABA pathway in rats. Interactions with adenosine A(2A) and dopamine D(2) receptors. Neurosci Lett 324:154–158

    Article  CAS  PubMed  Google Scholar 

  129. Carriba P, Ortiz O, Patkar K, Justinova Z, Stroik J, Themann A, Muller C, Woods AS, Hope BT, Ciruela F, Casado V, Canela EI, Lluis C, Goldberg SR, Moratalla R, Franco R, Ferre S (2007) Striatal adenosine A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids. Neuropsychopharmacology 32:2249–2259

    Article  CAS  PubMed  Google Scholar 

  130. Lee FS, Chao MV (2001) Activation of Trk neurotrophin receptors in the absence of neurotrophins. Proc Natl Acad Sci USA 98:3555–3560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Sebastiao AM, Ribeiro JA (2009) Triggering neurotrophic factor actions through adenosine A2A receptor activation: implications for neuroprotection. Br J Pharmacol 158:15–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Sebastiao AM, Ribeiro JA (2009) Adenosine receptors and the central nervous system. Hand Exp Pharmacol 193:471–534

    Article  CAS  Google Scholar 

  133. Mattson MP (2008) Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann N Y Acad Sci 1144:97–112. https://doi.org/10.1196/annals.1418.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Diogenes MJ, Fernandes CC, Sebastiao AM, Ribeiro JA (2004) Activation of adenosine A2A receptor facilitates brain-derived neurotrophic factor modulation of synaptic transmission in hippocampal slices. J Neurosci 24:2905–2913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Fontinha BM, Diogenes MJ, Ribeiro JA, Sebastiao AM (2008) Enhancement of long-termpotentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine. Neuropharmacology 54:924–933

    Article  CAS  PubMed  Google Scholar 

  136. Domenici MR, Scattoni ML, Martire A, Lastoria G, Potenza RL, Borioni A, Venerosi A, Calamandrei G, Popoli P (2007) Behavioral and electrophysiological effects of the adenosine receptor antagonist SCH 58261 in R6/2 Huntington’s disease mice. Neurobiol Dis 28:197–205

    Article  CAS  PubMed  Google Scholar 

  137. Dias RB, Ribeiro JA, Sabastiao AM (2012) Enhancement of AMPA currents and GluR1 membrane expression through PKA-coupled adenosine A2A receptors. Hippocampus 22:276–291

    Article  CAS  PubMed  Google Scholar 

  138. Fredholm BB (2011) Handbook of experimental pharmacology, vol 200. Springer, Berlin

    Google Scholar 

  139. Laska EM, Sunshine A, Mueller F, Elvers WB, Siegel C, Rubin A (1984) Caffeine as an analgesic adjuvant. JAMA 251:1711–1718

    Article  CAS  PubMed  Google Scholar 

  140. Fredholm BB (1978) effect of adenosine, adenosine analogues, and drugs inhibiting adenosine inactivation on lipolysis in rat fat cells. Acta Physiol Scand 102:191–198

    Article  CAS  PubMed  Google Scholar 

  141. Szkudelski T, Szkudelski K, Nogowski L (2009) Effect of adenosine a1 receptor antagonism on lpogenesis and lipolysis in isolated rat adipocytes. Physiol Res 58:863–871

    CAS  PubMed  Google Scholar 

  142. van Dam RM, Hu FB (2005) Coffee consumption and risk of type 2 diabetes; a systematic review. JAMA 294:97–104

    Article  PubMed  Google Scholar 

  143. Jime´nez-Jime´nez FJ, Mateo D, Gime´nez-Roldan S (1992) Premorbid smoking, alcohol consumption, and coffee drinking habits in Parkinson’s disease: a case-control study. Mov Disord 7:339–344

    Article  Google Scholar 

  144. Hellenbrand W, Seidler A, Robra B-P et al (1997) Smoking and Parkinson’s disease: a case control study in Germany. Int J Epidemiol 26:328–339

    Article  CAS  PubMed  Google Scholar 

  145. Fall P-A, Frederikson M, Axelson O, Grane´rus A-K (1999) Nutritional and occupational factors influencing the risk of Parkinson’s disease: a case-control study in southeastern Sweden. Mov Disord 14:28–37

    Article  CAS  PubMed  Google Scholar 

  146. Ross GW, Abbott RD, Petrovitch H (2000) Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 283:2674–2679

    Article  CAS  PubMed  Google Scholar 

  147. Ascherio A, Zhang SM, Hernan MA, Kawachi I, Colditz GA, Speizer FE, Willett WC (2001) Prospective study of caffeine consumption and risk of Parkinson’s disease in men and women. Ann Neurol 50:56–63

    Article  CAS  PubMed  Google Scholar 

  148. Larsson SC (2014) Coffee, tea, and cocoa and risk of stroke. Stroke 45:309–314

    Article  PubMed  Google Scholar 

  149. Smith AP (2009) Caffeine, cognitive failures and health in a non-working community sample. Hum Psychopharmacol 24:29–34

    Article  PubMed  Google Scholar 

  150. Grosso G, Micek A, Castellano S, Pajak A, Galvano F (2016) Coffee, tea, caffeine and risk of depression: a systematic review and dose-response meta-analysis of observational studies. Mol Nutr Food Res 60:223–234

    Article  CAS  PubMed  Google Scholar 

  151. Kawachi I, Willett WC, Colditz GA, Stampfer MJ, Speizer FE (1996) A prospective study of coffee drinking and suicide in women. Arch Intern Med 116:521–525

    Article  Google Scholar 

  152. Sachse KT, Jackson EK, Wisniewski SR, Gillespie DG, Puccio AM, Clark RS, Dixon CE, Kochanek PM (2008) Increases in cerebrospinal fluid caffeine concentration are associated with favorable outcome after severe traumatic brain injury in humans. J Cereb Blood Flow Metab 28:395–401

    Article  CAS  PubMed  Google Scholar 

  153. Travassos M, Santana J, Baldeiras I, Tsolaki M, Gkatzima O, Sermin G, Yener GG et al (2015) does caffeine consumption modify cerebrospinal fluid amyloid-b levels in patients with Alzheimer’s disease? J Alzheimers Dis 47:1069–1078

    Article  CAS  PubMed  Google Scholar 

  154. Jarvis MJ (1993) Does caffeine intake enhance absolute levels of cognitive performance? Psychopharmacology 110:45–52

    Article  CAS  PubMed  Google Scholar 

  155. Hernán MA, Takkouche B, Caamaño-Isorna F, Gestal-Otero JJ (2002) A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson’s disease. Ann Neurol 52:276–284

    Article  PubMed  Google Scholar 

  156. Costa J, Lunet N, Santos C, Santos J, Vaz-Carneiro A (2010) Caffeine exposure and the risk of Parkinson’s disease: a systematic review and meta-analysis of observational studies. J Alzheimers Dis 20(Suppl):221–238

    Article  CAS  Google Scholar 

  157. Qi H, Li S (2014) Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson’s disease. Geriatr Gerontol Int 14:430–439

    Article  PubMed  Google Scholar 

  158. Ascherio A, Chen H, Schwarzschild MA, Zhang SM, Colditz GA, Speizer FE (2003) Caffeine, postmenopausal estrogen, and risk of Parkinson’s disease. Neurology 60:790–795

    Article  CAS  PubMed  Google Scholar 

  159. Ascherio A, Weisskopf MG, O’Reilly EJ, McCullough ML, Calle EE, Rodriguez C, Thun MJ (2004) Coffee consumption, gender, and Parkinson’s disease mortality in the cancer prevention study II cohort: the modifying effects of estrogen. Am J Epidemiol 160:977–984

    Article  PubMed  Google Scholar 

  160. Patwardhan RV, Desmond PV, Johnson RF, Schenker S (1980) Impaired elimination of caffeine by oral contraceptive steroids. J Lab Clin Med 95:603–608

    CAS  PubMed  Google Scholar 

  161. Abernethy DR, Todd EL (1985) Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 28:425–428

    Article  CAS  PubMed  Google Scholar 

  162. Xu K, Xu Y, Brown-Jermyn D, Chen JF, Ascherio A, Dluzen DE, Schwarzschild MA (2006) Estrogen prevents neuroprotection by caffeine in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. J Neurosci 26:535–541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Xu K, Xu YH, Chen JF, Schwarzschild MA (2010) Neuroprotection by caffeine: time course and role of its metabolites in the MPTP model of Parkinson’s Disease. Neuroscience 167:475–481

    Article  CAS  PubMed  Google Scholar 

  164. Chen JF, Xu K, Petzer JP, Staal R, X YJ, Beilstein M, Sonsalla PK, Caatagnoli K, Castagnoli N, Schwarzschild MA (2001) Neuroprotection by caffeine and A2a adenosine receptor inactivation in a model of Parkinson’s disease. J Neurosci 21:1–6

    PubMed  PubMed Central  Google Scholar 

  165. Ikeda K, Kurokawa M, Aoyama S, Kuwana Y (2002) Neuroprotection by adenosine A2A receptor blockade in experimental models of Parkinson’s disease. J Neurochem 80:262–270

    Article  CAS  PubMed  Google Scholar 

  166. Kalda A, Yu L, Oxtas E, Chen JF (2006) Novel neuroprotection by caffeine and adenosine A2A receptor antagonists in animal models of Parkinson’s disease. J Neurol Sci 242:9–15

    Article  CAS  Google Scholar 

  167. Maia L, de Mendonça A (2002) Does caffeine intake protect from Alzheimer’s disease? Eur J Neurol 9:377–382

    Article  CAS  PubMed  Google Scholar 

  168. Lindsay J, Sykes E, McDowell I, Verreault R, Laurin D (2004) More than the epidemiology of Alzheimer’s disease: contributions of the Canadian Study of Health and Aging. Can J Psychiatry 49:83–91

    Article  PubMed  Google Scholar 

  169. Arendash GW, Schleif W, Rezai-Zadeh K, Jackson EK, Zacharia LC, Cracchiolo JR, Shippy D, Tan J (2006) Caffeine protects Alzheimer’s mice against cognitive impairment and reduces brain beta-amyloid production. Neuroscience 142:941–952

    Article  CAS  PubMed  Google Scholar 

  170. Arendash GW, Mori T, Cao C, Mamcarz M, Runfeldt M, Dickson A, Rezai-Zadeh K, Tane J, Citron BA, Lin X, Echeverria V, Potter H (2009) Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer’s disease mice. J Alzheimers Dis 17:661–680

    Article  CAS  PubMed  Google Scholar 

  171. Chu YF, Chang WH, Black RM, Liu JR, Sompol P, Chen Y, Wei H, Zhao Q, Cheng IH (2012) Crude caffeine reduces memory impairment and amyloid β(1–42) levels in an Alzheimer’s mouse model. Food Chem 135:2095–2102

    Article  CAS  PubMed  Google Scholar 

  172. Laurent C, Eddarkaoui S, Derisbourg M, Leboucher A, Demeyer D, Carrier S, Schneider M, Hamdane M, Muller CE, Bucee L, Blum D (2014) Beneficial effects of caffeine in a transgenic model of Alzheimer’s disease-like tau pathology. Neurobiol Aging 35:2079–2090

    Article  CAS  PubMed  Google Scholar 

  173. Laurent C, Burnouf S, Ferry B, Batalha VL, Coelho JE, Baqi Y, Malik E, Mariciniak E, Parrot S, Van der Jeugd A, Faivre E, Flaten V, Ledent C, D’Hooge R, Sergeant N, Hamdane M, Humez S, Müller CE, Lopes LV, Buée L, Blum D (2016) A2A adenosine receptor deletion is protective in a mouse model of Tauopathy. Mol Psychiatry 21:97–107

    Article  CAS  PubMed  Google Scholar 

  174. Pelligrino DA, Xu HL, Vetri F (2010) Caffeine and the control of cerebral hemodynamics. J Alzheimers Dis 20:S51-62

    Article  CAS  PubMed  Google Scholar 

  175. Klaassen EB, de Groot RH, Evers EA, Snel J, Veerman EC, Ligtenberg AJ, Jolles J, Veltman DJ (2013) The effect of caffeine on working memory load-related brain activation in middle-aged males. Neuropharmacology 64:160–167

    Article  CAS  PubMed  Google Scholar 

  176. Koppelstaetter F, Poeppel TD, Siedentopf CM, Ischebeck A, Verius M, Haala I, Mottaghy FM, Rhomberg P, Golaszewski S, Gotwald T, Lorenz IH, Kolbitsch C, Felber S, Krause BJ (2007) Does caffeine modulate verbal working memory processes? An fMRI study. Neuroimage 39:492–499

    Article  PubMed  Google Scholar 

  177. Haller S, Rodriguez C, Moser D, Toma S, Hofmeister J, Sinanaj I, Van De Ville D, Giannakopoulos P, Lovblad KO (2013) Acute caffeine administration impact on working memory-related brain activation and functional connectivity in the elderly: a BOLD and perfusion MRI study. Neuroscience 10364–10371

  178. Han ME, Kim HJ, Lee YS, Kim DH, Choi JT, Pan CS, Yoon S, Baek SY, Kim BS, Kim JB, Oh SO (2009) Regulation of cerebrospinal fluid production by caffeine consumption. BMC Neurosci 30:110

    Article  CAS  Google Scholar 

  179. Wostyn P, Van Dam D, Audenaert K, De Deyn PP (2011) Increased cerebrospinal fluid production as a possible mechanism underlying Caffeine’s protective effect against Alzheimer’s disease. Int J Alzheimers Dis. 2011:617420

    PubMed  PubMed Central  Google Scholar 

  180. Coffee and Caffeine Genetics Consortium, Cornelis MC, Byrne EM, et al. (2015) Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Mol Psychiatry. 20:647–656

    Article  CAS  Google Scholar 

  181. Cornelis MC, Kacprowski T, Menni C et al (2016) Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior. Hum Mol Genet 25:5472–5482

    CAS  PubMed  Google Scholar 

  182. Do TM, Noel-Hudson MS, Ribes S, Besengez C, Smirnova M, Cisternino S, Buyse M, Calon F, Chimini G, Chacun H, Scherrmann JM, Farinotti R, Bourasset F (2012) ABCG2- and ABCG4-mediated efflux of amyloid-β peptide 1–40 at the mouse blood-brain barrier. J Alzheimers Dis 30:155–166

    Article  CAS  PubMed  Google Scholar 

  183. Zhang W, Xiong H, Callaghan D, Liu H, Jones A, Pei K, Fatehi D, Brunette E, Stanimirovic D (2013) Blood-brain barrier transport of amyloid beta peptides in efflux pump knock-out animals evaluated by in vivo optical imaging. Fluids Barriers CNS 10:13. https://doi.org/10.1186/2045-8118-10-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Raimondo A, Rees MG, Gloyn AL (2015) Glucokinase regulatory protein: complexity at the crossroads of triglyceride and glucose metabolism. Curr Opin Lipidol 26:88–95. https://doi.org/10.1097/MOL.0000000000000155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Kolz M, Johnson T, Sanna S et al (2009) Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet 5:e1000504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Wang Y, Viscarra J, Kim SJ, Sul HS (2015) Transcriptional regulation of hepatic lipogenesis. Nat Rev Mol Cell Biol 16:678–689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Camandola S, Mattson MP (2017) Brain metabolism in health, aging, and neurodegeneration.EMBO J. 2017 Jun 1;36(11):1474–1492

  188. Nagahara AH, Tuszynski MH (2011) Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov 10:209–219

    Article  CAS  PubMed  Google Scholar 

  189. Yang X, Zou J, Hyde DR, Davidson LA, Wei X (2009) Stepwise maturation of apicobasal polarity of the neuroepithelium is essential for vertebrate neurulation. J Neurosci 29:11426–11440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Jo K, Derin R, Li M, Bredt DS (1999) Characterization of MALS/Velis-1, -2, and – 3: a family of mammalian LIN-7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex. J Neurosci 19:4189–4199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Bécamel C, Alonso G, Galéotti N, Demey E, Jouin P, Ullmer C, Dumuis A, Bockaert J, Marin P (2002) Synaptic multiprotein complexes associated with 5-HT(2C) receptors: a proteomic approach. EMBO J 21:2332–2342

    Article  PubMed  PubMed Central  Google Scholar 

  192. Leonoudakis D, Conti LR, Radeke CM, McGuire LM, Vandenberg CA (2004) A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. J Biol Chem 279:19051–19063

    Article  CAS  PubMed  Google Scholar 

  193. Lu AT, Hannon E, Levine ME, Crimmins EM, Lunnon K, Mill J, Geschwind DH, Horvath S (2017) Genetic architecture of epigenetic and neuronal ageing rates in human brain regions. Nat Commun 8:15353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Sokolov AN, Pavlova MA, Klosterhalfen S, Enck P (2013) Chocolate and the brain: neurobiological impact of cocoa flavanols on cognition and behavior. Neurosci Biobehav Rev 37:2445–2453

    Article  CAS  PubMed  Google Scholar 

  195. Walker JM, Klakotskaia D, Ajit D, Weisman GA, Wood WG, Sun GY, Serfozo P, Simonyi A, Schachtman TR (2015) Beneficial effects of dietary EGCG and voluntary exercise on behavior in an Alzheimer’s disease mouse model. J Alzheimers Dis 44:561–572

    Article  CAS  PubMed  Google Scholar 

  196. Jia N, Han K, Kong JJ, Zhang XM, Sha S, Ren GR, Cao YP (2013) (-)-Epigallocatechin-3-gallate alleviates spatial memory impairment in APP/PS1 mice by restoring IRS-1 signaling defects in the hippocampus. Mol Cell Biochem 380:211–218

    Article  CAS  PubMed  Google Scholar 

  197. Wang J, Ferruzzi MG, Ho L, Blount J, Janle EM, Gong B, Pan Y, Gowda GA, Raftery D, Arrieta-Cruz I, Sharma V, Cooper B, Lobo J, Simon JE, Zhang C, Cheng A, Qian X, Ono K, Teplow DB, Pavlides C, Dixon RA, Pasinetti GM (2012) Brain-targeted proanthocyanidin metabolites for Alzheimer’s disease treatment. J Neurosci 32:5144–5150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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This work was supported by the Intramural Research Program of the National Institute on Aging.

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Camandola, S., Plick, N. & Mattson, M.P. Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease. Neurochem Res 44, 214–227 (2019). https://doi.org/10.1007/s11064-018-2492-0

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