Role of striatal A2A receptor subpopulations in neurological disorders

Adenosine: A Key Link between Metabolism and Brain Activity

Volumn 9781461439035, Issue , 2013, Pages 179-197

  Ferré, Sergi ^a   Quiroz, César ^a   Orrú, Marco ^a   Guitart, Xavier ^a   Gulyani, Seema ^b   Allen, Richard ^b   Earley, Christopher J ^b  

^a NATIONAL INSTITUTE ON DRUG ABUSE   (United States)

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

Author keywords

Adenosine A2A receptor; Huntington disease; Parkinson's disease; Receptor heteromers; Restless Legs Syndrome; Striatum

Indexed keywords

EID: 84872412167     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4614-3903-5_9     Document Type: Chapter

References (97)

1. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J (2003) Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 4:101-119
2. Allen R (2004) Dopamine and iron in the pathophysiology of restless legs syndrome (RLS). Sleep Med 5:385-391
3. Allen RP, Walter AS, Montplaisir J, Hening W, Myers A, Bell TJ, Ferini-Strambi L (2005) Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 165:1286-1292
4. Andersson M, Usiello A, Borgkvist A, Pozzi L, Dominguez C, Fienberg AA, Svenningsson P, Fredholm BB, Borrelli E, Greengard P, Fisone G (2005) Cannabinoid action depends on phosphorylation of dopamine-and cAMP-regulated phosphoprotein of 32 kDa at the protein kinase A site in striatal projection neurons. J Neurosci 25:8432-8438
5. Angulo-Kinzler RM, Peirano P, Lin E, Algarin C, Garrido M, Lozoff B (2002) Twenty-four-hour motor activity in human infants with and without iron de fi ciency anemia. Early Hum Dev 70:85-101
6. Azdad K, Gall D, Woods AS, Ledent C, Ferré S, Schiffmann SN (2009) Dopamine D2 and adenosine A2A receptors regulate NMDA-excitation in accumbens neurons through A2A-D2 receptor heteromerization. Neuropsychopharmacology 34:972-986
7. Bauer A, Zilles K, Matusch A, Holzmann C, Riess O, von Hörsten S (2005) Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington's disease mutation. J Neurochem 94:639-650
8. Beard JL (2003) Iron de fi ciency alters brain development and functioning. J Nutr 133: 1468S-1472S
9. Beard JL, Connor JR (2003) Iron status and neural functioning. Annu Rev Nutr 23:41-58
10. Brooks DJ, Papapetropoulos S, Vandenhende F, Tomic D, He P, Coppell A, O'Neill G (2010) An open-label, positron emission tomography study to assess adenosine A2A brain receptor occupancy of vipadenant (BIIB014) at steady-state levels in healthy male volunteers. Clin Neuropharmacol 33:55-60
11. Cabello N, Gandia J, Bertarelli DC, Watanabe M, Lluis C, Franco R, Ferré S, Lujan R, Ciruela F (2009) Metabotropic glutamate type 5, dopamine D2 and adenosine A2A receptors form higher-order oligomers in living cells. J Neurochem 109:1497-1507
12. Calon F, Hadj Tahar A, Blanchet PJ, Morissette M, Grondin R, Goulet M, Doucet JP, Robertson GS, Nestler E, Di Paolo T, Bédard PJ (2000) Dopamine-receptor stimulation: biobehavioral and biochemical consequences. Trends Neurosci 23:S92-S100
13. Calon F, Birdi S, Rajput AH, Hornykiewicz O, Bédard PJ, Di Paolo T (2002) Increase of preproenkephalin mRNA levels in the putamen of Parkinson disease patients with levodopa-induced dyskinesias. J Neuropathol Exp Neurol 61:186-196
14. Calon F, Dridi M, Hornykiewicz O, Bédard PJ, Rajput AH, Di Paolo T (2004) Increased adenosine A2A receptors in the brain of Parkinson's disease patients with dyskinesias. Brain 127:1075-1084
15. Carriba P, Ortiz O, Patkar K, Justinova Z, Stroik J, Themann A, Müller C, Woods AS, Hope BT, Ciruela F, Casadó V, Canela EI, Lluis C, Goldberg SR, Moratalla R, Franco R, Ferré S (2007) Striatal adenosine A 2A and cannabinoid CB 1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids. Neuropsychopharmacology 32:2249-2259
16. Carriba P, Navarro G, Ciruela F, Ferré S, Casado V, Agnati LF, Cortes A, Mallol J, Fuxe K, Canela EI, Lluis C, Franco R (2008) Detection of heteromerization of more than two proteins by sequential BRET-FRET. Nat Methods 5:727-733
17. Cha JH, Frey AS, Alsdorf SA, Kerner JA, Kosinski CM, Mangiarini L, Penney JB Jr, Davies SW, Bates GP, Young AB (1999) Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease. Philos Trans R Soc Lond B Biol Sci 354:981-989
18. Chen JF, Moratalla R, Impagnatiello F, Grandy DK, Cuellar B, Rubinstein M, Beilstein MA, Hackett E, Fink JS, Low MJ, Ongini E, Schwarzschild MA (2001) The role of the D(2) dopamine receptor (D(2)R) in A(2A) adenosine receptor (A(2A)R)-mediated behavioral and cellular responses as revealed by A(2A) and D(2) receptor knockout mice. Proc Natl Acad Sci U S A 98:1970-1975
19. Ciruela F, Casado V, Rodrigues RJ, Luján R, Burgueno J, Canals M, Borycz J, Rebola N, Goldberg SR, Mallol J, Cortés A, Canela EI, López-Giménez JF, Milligan G, Lluis C, Cunha RA, Ferré S, Franco R (2006) Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. J Neurosci 26:2080-2087
20. Connor JR, Wang XS, Patton SM, Menzies SL, Troncoso JC, Earley CJ, Allen RP (2004) Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome. Neurology 62:1563-1567
21. Connor JR, Wang XS, Allen RP, Beard JL, Wiesinger JA, Felt BT, Earley CJ (2009) Altered dopaminergic pro fi le in the putamen and substantia nigra in Restless Leg Syndrome. Brain 132:2403-2412
22. Dhaenens CM, Burnouf S, Simonin C, Van Brussel E, Duhamel A, Defebvre L, Duru C, Vuillaume I, Cazeneuve C, Charles P, Maison P, Debruxelles S, Verny C, Gervais H, Azulay JP, Tranchant C, Bachoud-Levi AC, Dürr A, Buée L, Krystkowiak P, Sablonnière B, Blum D (2009) A genetic variation in the ADORA2A gene modi fi es age at onset in Huntington's disease. Neurobiol Dis 35:474-476
23. DeLong MR, Wichmann T (2007) Circuits and circuit disorders of the basal ganglia. Arch Neurol 64:20-24
24. Earley CJ, Connor JR, Beard JL, Malecki EA, Epstein DK, Allen RP (2000) Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology 54:1698-1700
25. Earley CJ, Barker PB, Horska A, Allen RP (2006) MRI-determined regional brain iron concentrations in early-and late-onset restless legs syndrome. Sleep Med 7:459-461
26. Erikson KM, Jones BC, Beard JL (2000) Iron de fi ciency alters dopamine transporter functioning in rat striatum. J Nutr 130:2831-2837
27. Erikson KM, Jones BC, Hess EJ, Zhang Q, Beard JL (2001) Iron de fi ciency decreases dopamine D1 and D2 receptors in rat brain. Pharmacol Biochem Behav 69:409-418
28. Factor S, Mark MH, Watts R, Struck L, Mori A, Ballerini R, Sussman NM, Istradefylline 6002-US-007 Study Group (2010) A long-term study of istradefylline in subjects with fl uctuating Parkinson's disease. Parkinsonism Relat Disord 16:423-426
29. Fernandez HH, Greeley DR, Zweig RM, Wojcieszek J, Mori A, Sussman NM, 6002-US-051 Study Group (2010) Istradefylline as monotherapy for Parkinson disease: results of the 6002-US-051 trial. Parkinsonism Relat Disord 16:16-20
30. Ferré S, Fuxe K, von Euler G, Johansson B, Fredholm BB (1992) Adenosine-dopamine interactions in the brain. Neuroscience 51:501-512
31. Ferré S, Popoli P, Gimenez-Llort L, Rimondini R, Müller CE, Stromberg I, Ogren SO, Fuxe K (2001) Adenosine/dopamine interaction: implications for the treatment of Parkinson's disease. Parkinsonism Relat Disord 7:235-241
32. Ferré S, Karcz-Kubicha M, Hope BT, Popoli P, Burgueno J, Casado V, Fuxe K, Lluis C, Goldberg SR, Franco R, Ciruela F (2002) Synergistic interaction between adenosine A 2A and glutamate mGlu 5 receptors: Implications for striatal neuronal function. 99:11940-11945
33. Ferré S, Ciruela F, Woods AS, Lluis C, Franco R (2007) Functional relevance of neurotransmitter receptor heteromers in the central nervous system. Trends Neurosci 30:440-446
34. Ferré S, Quiroz C, Woods AS, Cunha R, Popoli P, Ciruela F, Lluis C, Franco R, Azdad K, Schiffmann SN (2008) An update on adenosine A2A-dopamine D2 receptor interactions. Implications for the function of G protein-coupled receptors. Curr Pharm Des 14:1468-1474
35. Ferré S, Baler R, Bouvier M, Caron MG, Devi LA, Durroux T, Fuxe K, George SR, Javitch JA, Lohse MJ, Mackie K, Milligan G, P fl eger KDG, Pin J-P, Volkow N, Waldhoer M, Woods AS, Franco R (2009) Building a new conceptual framework for receptor heteromers. Nat Chem Biol 5:131-134
36. Ferré S, Lluis C, Justinova Z, Quiroz C, Orru M, Navarro G, Canela EI, Franco R, Goldberg SR (2010) Adenosine-cannabinoid receptor interactions. Implications for striatal function. Br J Pharmacol 160:443-453
37. Fiorentini C, Busi C, Gorruso E, Gotti C, Spano P, Missale C (2008) Reciprocal regulation of dopamine D1 and D3 receptor function and traf fi cking by heterodimerization. Mol Pharmacol 74:59-69
38. Glass M, Dragunow M, Faull RL (2000) The pattern of neurodegeneration in Huntington's disease: A comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington's disease. Neuroscience 97:505-519
39. Grondin R, Bédard PJ, Hadj Tahar A, Grégoire L, Mori A, Kase H (1999) Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys. Neurology 52:1673-1677
40. Gulyani S, Earley CJ, Camandola S, Maudsley S, Ferré S, Mughal MR, Martin B, Cheng A, Gleichmann M, Jones BC, Allen RP, Mattson MP (2009) Diminished iron concentrations increase adenosine A(2A) receptor levels in mouse striatum and cultured human neuroblastoma cells. Exp Neurol 215:236-242
41. Håkansson K, Galdi S, Hendrick J, Snyder G, Greengard P, Fisone G (2006) Regulation of phosphorylation of the GluR1 AMPA receptor by dopamine D2 receptors. J Neurochem 96:482-488
42. Hauser RA, Hubble JP, Truong DD, Istradefylline US-001 Study Group (2003) Randomized trial of the adenosine A(2A) receptor antagonist istradefylline in advanced PD. Neurology 61:297-303
43. Hettinger BD, Lee A, Linden J, Rosin DL (1998) Ultrastructural localization of adenosine A2A receptors suggests multiple cellular sites for modulation of GABAergic neurons in rat striatum. J Comp Neurol 431:331-346
44. Higley MJ, Sabatini BL (2010) Competitive regulation of synaptic Ca2+ in fl ux by D2 dopamine and A2A adenosine receptors. Nat Neurosci 13:958-966
45. 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, Ferré S, Fuxe K (2002) Coaggregation, cointernalization and codesensitization of adenosine A 2A receptors and dopamine D 2 receptors. J Biol Chem 277:18091-18097
46. James S, Richardson PJ (1993) The subcellular distribution of [3H]-CGS 21680 binding sites in the rat striatum: copuri fi cation with cholinergic nerve terminals. Neurochem Int 23:115-122
47. Jin S, Johansson B, Fredholm BB (1993) Effects of adenosine A1 and A2 receptor activation on electrically evoked dopamine and acetylcholine release from rat striatal slices. J Pharmacol Exp Ther 267:801-808
48. Justinova Z, Ferré S, Redhi GH, Mascia P, Stroik J, Quarta D, Yasar S, Muller CE, Franco R, Goldberg SR (2010) Reinforcing and neurochemical effects of cannabinoid CB1 receptor agonists, but not cocaine, are altered by an adenosine A2A receptor antagonist. Addict Biol 16:405-415
49. Kachroo A, Orlando LR, Grandy DK, Chen JF, Young AB, Schwarzschild MA (2005) Interactions between metabotropic glutamate 5 and adenosine A2A receptors in normal and parkinsonian mice. J Neurosci 25:10414-10419
50. Kanda T, Jackson MJ, Smith LA, Pearce RK, Nakamura J, Kase H, Kuwana Y, Jenner P (2000) Combined use of the adenosine A(2A) antagonist KW-6002 with L-DOPA or with selective D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTPtreated monkeys. Exp Neurol 162:321-327
51. Kull B, Ferré S, Arslan G, Svenningsson P, Fuxe K, Owman C, Fredholm BB (1999) Reciprocal interactions between adenosine A 2A and dopamine D 2 receptors in CHO cells co-transfected with the two receptors. Biochem Pharmacol 58:1035-1045
52. Lerner TN, Horne EA, Stella N, Kreitzer AC (2010) Endocannabinoid signaling mediates psychomotor activation by adenosine A2A antagonists. J Neurosci 30:2160-2164
53. LeWitt PA, Guttman M, Tetrud JW, Tuite PJ, Mori A, Chaikin P, Sussman NM, 6002-US-005 Study Group (2008) Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces "off" time in Parkinson's disease: A double-blind, randomized, multicenter clinical trial (6002-US-005). Ann Neurol 63:295-302
54. Lozoff B, Georgieff MK (2006) Iron de fi ciency and brain development. Semin Pediatr Neurol 13:158-165
55. Martire A, Tebano MT, Chiodi V, Ferreira SG, Cunha RA, Köfalvi A, Popoli P (2011) Pre-synaptic adenosine A2A receptors control cannabinoid CB1 receptor-mediated inhibition of striatal glutamatergic neurotransmission. J Neurochem 116:273-280
56. Mizuno Y, Hasegawa K, Kondo T, Kuno S, Yamamoto M, Japanese Istradefylline Study Group (2010) Clinical ef fi cacy of istradefylline (KW-6002) in Parkinson's disease: A randomized, controlled study. Mov Disord 25:1437-1443
57. Moresco RM, Todde S, Belloli S, Simonelli P, Panzacchi A, Rigamonti M, Galli-Kienle M, Fazio F (2005) In vivo imaging of adenosine A2A receptors in rat and primate brain using [11C] SCH442416. Eur J Nucl Med Mol Imaging 32:405-413
58. Morissette M, Goulet M, Soghomonian JJ, Blanchet PJ, Calon F, Bédard PJ, Di Paolo T (1997) Preproenkephalin mRNA expression in the caudate-putamen of MPTP monkeys after chronic treatment with the D2 agonist U91356A in continuous or intermittent mode of administration: comparison with L-DOPA therapy. Brain Res Mol Brain Res 49:55-62
59. Navarro G, Ferré S, Cordomi A, Moreno E, Mallol J, Casadó V, Cortés A, Hoffmann H, Ortiz J, Canela EI, Lluís C, Pardo L, Franco R, Woods AS (2010) Interactions between intracellular domains as key determinants of the quaternary structure and function of receptor heteromers. J Biol Chem 285:27346-27359
60. Nelson C, Erikson K, Piñero DJ, Beard JL (1997) In vivo dopamine metabolism is altered in ironde fi cient anemic rats. J Nutr 127:2282-2288
61. Nguyen HP, Kobbe P, Rahne H, Wörpel T, Jäger B, Stephan M, Pabst R, Holzmann C, Riess O, Korr H, Kántor O, Petrasch-Parwez E, Wetzel R, Osmand A, von Hörsten S (2006) Behavioral abnormalities precede neuropathological markers in rats transgenic for Huntington's disease. Hum Mol Genet 15:3177-3194
62. Nishi A, Liu F, Matsuyama S, Hamada M, Higashi H, Nairn AC, Greengard P (2003) Metabotropic mGlu5 receptors regulate adenosine A2A receptor signaling. Proc Natl Acad Sci U S A 100:1322-1327
63. Nordlander NB (1954) Restless Legs. Brit J Phys Med 17:160-162
64. Obeso JA, Rodríguez-Oroz MC, Rodríguez M, Arbizu J, Giménez-Amaya JM (2002) The basal ganglia and disorders of movement: pathophysiological mechanisms. News Physiol Sci 17:51-55
65. Orrú M, Quiroz C, Guitart X, Ferré S (2011a) Pharmacological evidence for different populations of postsynaptic adenosine A2A receptors in the rat striatum. Neuropharmacology 61:967-974
66. Orrú M, Bakešová J, Brugarolas M, Quiroz C, Beaumont V, Goldberg SR, Lluís C, Cortés A, Franco R, Casadó V, Canela EI, Ferré S (2011b) Striatal Pre-and Postsynaptic Pro fi le of Adenosine A(2A) Receptor Antagonists. PLoS One 6:e16088
67. Orrú M, Zanoveli JM, Quiroz C, Nguyen HP, Guitart X, Ferré S (2011c) Functional changes in postsynaptic adenosine A(2A) receptors during early stages of a rat model of Huntington disease. Exp Neurol 232:76-80
68. Popoli P, Betto P, Reggio R, Ricciarello G (1995) Adenosine A2A receptor stimulation enhances striatal extracellular glutamate levels in rats. Eur J Pharmacol 287:215-217
69. Popoli P, Pezzola A, Torvinen M, Reggio R, Pintor A, Scarchili L, Fuxe K, Ferré S (2001) The selective mGlu5 receptor agonist CHPG inhibits quinpirole-induced turning in 6-hydroxydopaminelesioned rats and modulates the binding characteristics of dopamine D 2 receptors in the rat striatum: Interactions with adenosine A 2A receptors. Neuropsychopharmacology 25:505-513
70. Popoli P, Blum D, Martire A, Ledent C, Ceruti S, Abbracchio MP (2007) Functions, dysfunctions and possible therapeutic relevance of adenosine A2A receptors in Huntington's disease. Prog Neurobiol 81:331-348
71. Preston Z, Lee K, Widdowson L, Freeman TC, Dixon AK, Richardson PJ (2000) Adenosine receptor expression and function in rat striatal cholinergic interneurons. Br J Pharmacol 130: 886-890
72. Quiroz C, Lujan R, Uchigashima M, Simoes AP, Lerner TN, Borycz J, Kachroo A, Canas PM, Orru M, Schwarzschild MA, Rosin DL, Kreitzer AC, Cunha RA, Watanabe M, Ferré S (2009) Key modulatory role of presynaptic adenosine A 2A receptors in cortical neurotransmission to the striatal direct pathway. Scienti fi cWorldJournal 9:1321-1344
73. Quiroz C, Pearson V, Gulyani S, Allen R, Earley C, Ferré S (2010) Up-regulation of striatal adenosine A 2A receptors with iron de fi ciency in rats. Effects on locomotion and cortico-striatal neurotransmission. Exp Neurol 224:292-298
74. Ramlackhansingh AF, Bose SK, Ahmed I, Turkheimer FE, Pavese N, Brooks DJ (2011) Adenosine 2A receptor availability in dyskinetic and nondyskinetic patients with Parkinson disease. Neurology 76:1811-1816
75. Ravikumar B, Vacher C, Berger Z (2004) Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fl y and mouse models of Huntington disease. Nat Genet 36:585-595
76. Rodrigues RJ, Alfaro TM, Rebola N, Oliveira CR, Cunha RA (2005) Co-localization and functional interaction between adenosine A(2A) and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum. J Neurochem 92:433-441
77. Rosin DL, Robeva A, Woodard RL, Guyenet PG, Linden J (1998) Immunohistochemical localization of adenosine A2A receptors in the rat central nervous system. J Comp Neurol 401:163-186
78. Schiffmann SN, Fisone G, Moresco R, Cunha R, Ferré S (2007) Adenosine A2A receptors and basal ganglia physiology. Prog Neurobiol 83:277-292
79. Shen HY, Coelho JE, Ohtsuka N, Canas PM, Day YJ, Huang QY, Rebola N, Yu L, Boison D, Cunha RA, Linden J, Tsien JZ, Chen JF (2008) A critical role of the adenosine A2A receptor in extrastriatal neurons in modulating psychomotor activity as revealed by opposite phenotypes of striatum and forebrain A2A receptor knock-outs. J Neurosci 28:2970-2975
80. Soria G, Castañé A, Ledent C, Parmentier M, Maldonado R, Valverde O (2004) Adenosine A2A receptors are involved in physical dependence and place conditioning induced by THC. Eur J Neurosci 20:2203-2213
81. Taherzadeh-Fard E, Saft C, Wieczorek S, Epplen JT, Arning L (2010) Age at onset in Huntington's disease: replication study on the associations of ADORA2A, HAP1 and OGG1. Neurogenetics 11:435-439
82. Tanganelli S, Sandager-Nielsen K, Ferraro L, Antonelli T, Kehr J, Franco R, Ferré S, Agnati LF, Fuxe K, Scheel-Krüger J (2004) Striatal plasticity at the network level. Focus on adenosine A2A and D2 interactions in models of Parkinson's disease. Parkinsonism Relat Disord 10:273-280
83. Tarditi A, Camurri A, Varani K, Borea PA, Woodman B, Bates G, Cattaneo E, Abbracchio MP (2006) Early and transient alteration of adenosine A 2A receptor signaling in a mouse model of Huntington disease. Neurobiol Dis 23:44-53
84. Tebano MT, Martire A, Chiodi V, Pepponi R, Ferrante A, Domenici MR, Frank C, Chen JF, Ledent C, Popoli P (2009) Adenosine A2A receptors enable the synaptic effects of cannabinoid CB1 receptors in the rodent striatum. J Neurochem 110:1921-1930
85. Tergau F, Wische S, Paulus W (1999) Motor system excitability in patients with Restless Legs Syndrome. Neurology 52:1060-1063
86. Tozzi A, de Iure A, Di Filippo M, Tantucci M, Costa C, Borsini F, Ghiglieri V, Giampà C, Fusco FR, Picconi B, Calabresi P (2011) The distinct role of medium spiny neurons and cholinergic interneurons in the D 2 /A 2 A receptor interaction in the striatum: implications for Parkinson's disease. J Neurosci 31:1850-1862
87. Unger EL, Wiesinger JA, Hao L, Beard JL (2008) Dopamine D2 receptor expression is altered by changes in cellular iron levels in PC12 cells and rat brain tissue. J Nutr 138:2487-2494
88. Varani K, Rigamonti D, Sipione S, Camurri A, Borea PA, Cattabeni F, Abbracchio MP, Cattaneo E (2001) Aberrant ampli fi cation of A 2A receptor signaling in striatal cells expressing mutant huntingtin. FASEB J 15:1245-1247
89. Varani K, Abbrachio MP, Cannella M, Cislaghi G, Giallonardo P, Mariotti C, Cattabriga E, Borea PA, Squitieri F, Cattaneo E (2003) Aberrant A 2A receptor function in peripheral blood cells in Huntington's disease. FASEB J 17:2148-2150
90. Varani K, Vincenzi F, Tosi A, Gessi S, Casetta I, Granieri G, Fazio P, Leung E, MacLennan S, Granieri E, Borea PA (2010) A2A adenosine receptor overexpression and functionality, as well as TNF-alpha levels, correlate with motor symptoms in Parkinson's disease. FASEB J 24:587-598
91. von Hörsten S, Schmitt I, Nguyen HP, Holzmann C, Schmidt T, Walther T, Bader M, Pabst R, Kobbe P, Krotova J, Stiller D, Kask A, Vaarmann A, Rathke-Hartlieb S, Schulz JB, Grasshoff U, Bauer I, Vieira-Saecker AM, Paul M, Jones L, Lindenberg KS, Landwehrmeyer B, Bauer A, Li XJ, Riess O (2003) Transgenic rat model of Huntington's disease. Hum Mol Genet 12:617-624
92. Weinberg J, Dallman PR, Levine S (1980) Iron de fi ciency during early development in the rat: behavioral and physiological consequences. Pharmacol Biochem Behav 12:493-502
93. Wellington CL, Leavitt BR, Hayden MR (2000) Huntington disease: new insights on the role of huntingtin cleavage. J Neural Transm Suppl 58:1-17
94. Yang W, Dunlap JR, Andrews RB, Wetzel R (2002) Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells. Hum Mol Genet 11:2905-2917
95. Yao L, Fan P, Jiang Z, Mailliard WS, Gordon AS, Diamond I (2003) Addicting drugs utilize a synergistic molecular mechanism in common requiring adenosine and Gi-beta gamma dimers. Proc Natl Acad Sci U S A 100:14379-14384
96. Youdim MB, Ben-Shachar D, Ashkenazi R, Yehuda S (1983) Brain iron and dopamine receptor function. Adv Biochem Psychopharmacol 37:309-321
97. Zeng BY, Pearce RK, MacKenzie GM, Jenner P (2000) Alterations in preproenkephalin and adenosine-2a receptor mRNA, but not preprotachykinin mRNA correlate with occurrence of dyskinesia in normal monkeys chronically treated with L-DOPA. Eur J Neurosci 12:1096-1104