, a mouse model of Huntington's disease, Neuron, vol.33, pp.849-860, 2002.

C. Cepeda, M. A. Ariano, and C. R. Calvert, NMDA receptor function in mouse models of Huntington disease, J Neurosci Res, vol.66, pp.525-539, 2001.

A. Ferrante, A. Martire, and M. Armida, Influence of CGS 21680, a selective adenosine A(2A) receptor agonist, on NMDA receptor function and expression in the brain of Huntington's disease mice, Brain Res, vol.1323, pp.184-191, 2010.

A. Martire, A. Ferrante, and R. L. Potenza, Remodeling of striatal NMDA receptors by chronic A(2A) receptor blockade in Huntington's disease mice, Neurobiol Dis, vol.37, pp.99-105, 2010.

J. Shehadeh, H. B. Fernandes, Z. Mullins, and M. M. , Striatal neuronal apoptosis is preferentially enhanced by NMDA receptor activation in YAC transgenic mouse model of Huntington disease, Neurobiol Dis, vol.21, pp.392-403, 2006.

A. J. Milnerwood, C. M. Gladding, and M. A. Pouladi, Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice, Neuron, vol.65, pp.178-190, 2010.

D. Blum, M. C. Galas, and A. Pintor, A dual role of adenosine A2A receptors in 3-nitropropionic acid-induced striatal lesions: Implications for the neuroprotective potential of A2A antagonists, J Neurosci, vol.23, pp.5361-5369, 2003.

P. Popoli, A. Pintor, and M. R. Domenici, Blockade of striatal adenosine A2A receptor reduces, through a presynaptic mechanism, quinolinic acid-induced excitotoxicity: Possible relevance to neuroprotective interventions in neurodegenerative diseases of the striatum, J Neurosci, vol.22, pp.1967-1975, 2002.

M. F. Beal, N. W. Kowall, D. W. Ellison, M. F. Mazurek, K. J. Swartz et al., Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid, Nature, vol.321, pp.168-171, 1986.

P. Guidetti, R. E. Luthi-carter, S. J. Augood, and R. Schwarcz, Neostriatal and cortical quinolinate levels are increased in early grade Huntington's disease, Neurobiol Dis, vol.17, pp.455-461, 2004.

P. Guidetti, G. P. Bates, and R. K. Graham, Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice, Neurobiol Dis, vol.23, pp.190-197, 2006.
DOI : 10.1016/j.nbd.2006.02.011

E. Brouillet, F. Conde, M. F. Beal, and P. Hantraye, Replicating Huntington's disease phenotype in experimental animals, Prog Neurobiol, vol.59, pp.427-468, 1999.

G. Liot, J. Valette, J. Pépin, J. Flament, and E. Brouillet, Energy defects in Huntington's disease: Why ''in vivo'' evidence matters, Biochem Biophys Res Commun, vol.483, pp.1084-1095, 2017.

B. G. Jenkins, H. D. Rosas, and Y. C. Chen, 1H NMR spectroscopy studies of Huntington's disease: Correlations with CAG repeat numbers, Neurology, vol.50, pp.1357-1365, 1998.

S. E. Browne, A. C. Bowling, and U. Macgarvey, Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia, Ann Neurol, vol.41, pp.646-653, 1997.

M. Gu, M. T. Gash, V. M. Mann, F. Javoy-agid, J. M. Cooper et al., Mitochondrial defect in Huntington's disease caudate nucleus, Ann Neurol, vol.39, pp.385-389, 1996.

S. J. Tabrizi, M. W. Cleeter, J. Xuereb, J. W. Taanman, J. M. Cooper et al., Biochemical abnormalities and excitotoxicity in Huntington's disease brain, Ann Neurol, vol.45, pp.25-32, 1999.

A. Benchoua, Y. Trioulier, and D. Zala, Involvement of mitochondrial complex II defects in neuronal death produced by N-terminus fragment of mutated huntingtin, Mol Biol Cell, vol.17, pp.1652-1663, 2006.

A. Benchoua, Y. Trioulier, and E. Diguet, Dopamine determines the vulnerability of striatal neurons to the N-terminal fragment of mutant huntingtin through the regulation of mitochondrial complex II, Hum Mol Genet, vol.17, pp.1446-1456, 2008.

A. V. Panov, C. A. Gutekunst, and B. R. Leavitt, Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines, Nat Neurosci, vol.5, pp.731-736, 2002.

J. Kim, J. P. Moody, and C. K. Edgerly, Mitochondrial loss, dysfunction and altered dynamics in Huntington's disease, Hum Mol Genet, vol.19, pp.3919-3935, 2010.

P. Weydt, V. V. Pineda, and A. E. Torrence, Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration, Cell Metab, vol.4, pp.349-362, 2006.

U. Shirendeb, A. P. Reddy, and M. Manczak, Abnormal mitochondrial dynamics, mitochondrial loss and mutant huntingtin oligomers in Huntington's disease: Implications for selective neuronal damage, Hum Mol Genet, vol.20, pp.1438-1455, 2011.

T. Milakovic and G. V. Johnson, Mitochondrial respiration and ATP production are significantly impaired in striatal cells expressing mutant huntingtin, J Biol Chem, vol.280, pp.30773-30782, 2005.

I. S. Seong, E. Ivanova, and J. M. Lee, HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism, Hum Mol Genet, vol.14, pp.2871-2880, 2005.

Y. S. Choo, G. V. Johnson, and M. Macdonald, Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release, Hum Mol Genet, vol.13, pp.1407-1420, 2004.

X. Guo, M. H. Disatnik, M. Monbureau, M. Shamloo, D. Mochly-rosen et al., Inhibition of mitochondrial fragmentation diminishes Huntington's disease-associated neurodegeneration, J Clin Invest, vol.123, pp.5371-5388, 2013.

C. F. Lee and Y. Chern, Adenosine receptors and Huntington's disease, Int Rev Neurobiol, vol.119, pp.195-232, 2014.

T. C. Ju, H. M. Chen, and J. T. Lin, Nuclear translocation of AMPK-alpha1 potentiates striatal neurodegeneration in Huntington's disease, J Cell Biol, vol.194, pp.209-227, 2011.

J. T. Lin, W. C. Chang, and H. M. Chen, Regulation of feedback between protein kinase A and the proteasome system worsens Huntington's disease, Mol Cell Biol, vol.33, pp.1073-1084, 2013.

M. V. Chao, Neurotrophins and their receptors: A convergence point for many signalling pathways, Nat Rev Neurosci, vol.4, pp.299-309, 2003.

C. Zuccato and E. Cattaneo, Role of brain-derived neurotrophic factor in Huntington's disease, Prog Neurobiol, vol.81, pp.294-330, 2007.

C. Zuccato, A. Ciammola, and D. Rigamonti, Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease, Science, vol.293, pp.493-498, 2001.

C. Zuccato, M. Tartari, and A. Crotti, Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes, Nat Genet, vol.35, pp.76-83, 2003.

J. P. Dompierre, J. D. Godin, and B. C. Charrin, Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation, J Neurosci, vol.27, pp.3571-3583, 2007.

D. Del-toro, J. M. Canals, S. Gines, M. Kojima, G. Egea et al., Mutant huntingtin impairs the post-Golgi trafficking of brain-derived neurotrophic factor but not its Val66Met polymorphism, J Neurosci, vol.26, pp.12748-12757, 2006.

L. L. Wu, Y. Fan, S. Li, X. J. Li, and X. F. Zhou, Huntingtinassociated protein-1 interacts with pro-brain-derived neurotrophic factor and mediates its transport and release, J Biol Chem, vol.285, pp.5614-5623, 2010.

M. Borrell-pagès, J. M. Canals, and F. P. Cordelières, Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase, J Clin Invest, vol.116, pp.1410-1424, 2006.

G. Lynch, E. A. Kramar, and C. S. Rex, Brain-derived neurotrophic factor restores synaptic plasticity in a knockin mouse model of Huntington's disease, J Neurosci, vol.27, pp.4424-4434, 2007.

K. Gharami, Y. Xie, J. J. An, S. Tonegawa, and B. Xu, Brainderived neurotrophic factor over-expression in the forebrain ameliorates Huntington's disease phenotypes in mice, J Neurochem, vol.105, pp.369-379, 2008.

Q. Peng, N. Masuda, and M. Jiang, The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/2 Huntington's disease mouse model, Exp Neurol, vol.210, pp.154-163, 2008.

D. A. Simmons, C. S. Rex, and L. Palmer, Up-regulating BDNF with an ampakine rescues synaptic plasticity and memory in Huntington's disease knockin mice, Proc Natl Acad Sci USA, vol.106, pp.4906-4911, 2009.

A. Giralt, H. C. Friedman, and B. Caneda-ferron, BDNF regulation under GFAP promoter provides engineered astrocytes as a new approach for long-term protection in Huntington's disease, Gene Ther, vol.17, pp.1294-1308, 2010.

Y. Xie, M. R. Hayden, and B. Xu, BDNF overexpression in the forebrain rescues Huntington's disease phenotypes in YAC128 mice, J Neurosci, vol.30, pp.14708-14718, 2010.

A. L. Goldberg, Protein degradation and protection against misfolded or damaged proteins, Nature, vol.426, pp.895-899, 2003.

J. F. Gusella and M. E. Macdonald, Huntington's disease: Seeing the pathogenic process through a genetic lens, Trends Biochem Sci, vol.31, pp.533-540, 2006.

R. R. Kopito, Aggresomes, inclusion bodies and protein aggregation, Trends Cell Biol, vol.10, pp.524-530, 2000.

G. N. Demartino and T. G. Gillette, Proteasomes: Machines for all reasons, Cell, vol.129, pp.659-662, 2007.

A. Hershko and A. Ciechanover, The ubiquitin system, Annu Rev Biochem, vol.67, pp.425-479, 1998.

E. J. Bennett, T. A. Shaler, and B. Woodman, Global changes to the ubiquitin system in Huntington's disease, Nature, vol.448, pp.704-708, 2007.

S. Finkbeiner and S. Mitra, The ubiquitin-proteasome pathway in Huntington's disease, ScientificWorldJournal, vol.8, pp.421-433, 2008.

Z. Ortega and J. J. Lucas, Ubiquitin-proteasome system involvement in Huntington's disease. Front Mol Neurosci, vol.7, p.77, 2014.

H. Seo, K. C. Sonntag, and O. Isacson, Generalized brain and skin proteasome inhibition in Huntington's disease, Ann Neurol, vol.56, pp.319-328, 2004.

J. Wang, C. E. Wang, A. Orr, S. Tydlacka, S. H. Li et al., Impaired ubiquitin-proteasome system activity in the synapses of Huntington's disease mice, J Cell Biol, vol.180, pp.1177-1189, 2008.

Q. Zheng, T. Huang, and L. Zhang, Dysregulation of ubiquitin-proteasome system in neurodegenerative diseases, Front Aging Neurosci, vol.8, p.303, 2016.

H. Seo, K. C. Sonntag, W. Kim, E. Cattaneo, and O. Isacson, Proteasome activator enhances survival of Huntington's disease neuronal model cells, PLoS One, vol.2, p.238, 2007.

H. K. Wong, P. O. Bauer, and M. Kurosawa, Blocking acidsensing ion channel 1 alleviates Huntington's disease pathology via an ubiquitin-proteasomesystem-dependent mechanism, Hum Mol Genet, vol.17, pp.3223-3235, 2008.

H. Jia, R. J. Kast, J. S. Steffan, and E. A. Thomas, Selective histone deacetylase (HDAC) inhibition imparts beneficial effects in Huntington's disease mice: Implications for the ubiquitin-proteasomal and autophagy systems, Hum Mol Genet, vol.21, pp.5280-5293, 2012.

W. Kim and H. Seo, Baclofen, a GABAB receptor agonist, enhances ubiquitin-proteasome system functioning and neuronal survival in Huntington's disease model mice, Biochem Biophys Res Commun, vol.443, pp.706-711, 2014.

Y. Liu, C. L. Hettinger, D. Zhang, K. Rezvani, X. Wang et al., Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington's disease, J Neurochem, vol.129, pp.539-547, 2014.

J. Jeon, W. Kim, J. Jang, O. Isacson, and H. Seo, Gene therapy by proteasome activator, PA28gamma, improves motor coordination and proteasome function in Huntington's disease YAC128 mice, Neuroscience, vol.324, pp.20-28, 2016.

R. A. Nixon, The role of autophagy in neurodegenerative disease, Nat Med, vol.19, pp.983-997, 2013.

A. Gelman, M. Rawet-slobodkin, and Z. Elazar, Huntingtin facilitates selective autophagy, Nat Cell Biol, vol.17, pp.214-215, 2015.
DOI : 10.1038/ncb3125

Y. N. Rui, Z. Xu, and B. Patel, Huntingtin functions as a scaffold for selective macroautophagy, Nat Cell Biol, vol.17, pp.262-275, 2015.

Y. Kiriyama and H. Nochi, The function of autophagy in neurodegenerative diseases, Int J Mol Sci, vol.16, pp.26797-26812, 2015.

M. Martinez-vicente, Z. Talloczy, and E. Wong, Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease, Nat Neurosci, vol.13, pp.567-576, 2010.

S. Sarkar, E. O. Perlstein, and S. Imarisio, Small molecules enhance autophagy and reduce toxicity in Huntington's disease models, Nat Chem Biol, vol.3, pp.331-338, 2007.

A. Williams, S. Sarkar, and P. Cuddon, Nove targets for Huntington's disease in an mTOR-independent autophagy pathway, Nat Chem Biol, vol.4, pp.295-305, 2008.

H. Koga, M. Martinez-vicente, E. Arias, S. Kaushik, D. Sulzer et al., Constitutive upregulation of chaperone-mediated autophagy in Huntington's disease, J Neurosci, vol.31, pp.18492-18505, 2011.

D. D. Martin, S. Ladha, D. E. Ehrnhoefer, and M. R. Hayden, Autophagy in Huntington disease and huntingtin in autophagy, Trends Neurosci, vol.38, pp.26-35, 2015.

Z. X. Yu, S. H. Li, J. Evans, A. Pillarisetti, H. Li et al., Mutant huntingtin causes context-dependent neurodegeneration in mice with Huntington's disease, J Neurosci, vol.23, pp.2193-2202, 2003.

H. Y. Hsiao and Y. Chern, Targeting glial cells to elucidate the pathogenesis of Huntington's disease. Mol Neurobiol, vol.41, pp.248-255, 2010.

W. Lee, R. C. Reyes, and M. K. Gottipati, Enhanced Ca(2+)-dependent glutamate release from astrocytes of the BACHD Huntington's disease mouse model, Neurobiol Dis, vol.58, pp.192-199, 2013.

S. Y. Chou, J. Y. Weng, and H. L. Lai, Expandedpolyglutamine huntingtin protein suppresses the secretion and production of a chemokine (CCL5/RANTES) by astrocytes, J Neurosci, vol.28, pp.3277-3290, 2008.

J. Bradford, J. Y. Shin, and M. Roberts, Mutant huntingtin in glial cells exacerbates neurological symptoms of Huntington disease mice, J Biol Chem, vol.285, pp.10653-10661, 2010.

H. Y. Hsiao, Y. C. Chen, H. M. Chen, P. H. Tu, and Y. Chern, A critical role of astrocyte-mediated nuclear factorkappaB-dependent inflammation in Huntington's disease, Hum Mol Genet, vol.22, pp.1826-1842, 2013.

A. Crotti, C. Benner, and B. E. Kerman, Mutant Huntingtin promotes autonomous microglia activation via myeloid lineage-determining factors, Nat Neurosci, vol.17, pp.513-521, 2014.

B. Huang, W. Wei, and G. Wang, Mutant huntingtin downregulates myelin regulatory factor-mediated myelin gene expression and affects mature oligodendrocytes, Neuron, vol.85, pp.1212-1226, 2015.

W. J. Powers, T. O. Videen, and J. Markham, Selective defect of in vivo glycolysis in early Huntington's disease striatum, Proc Natl Acad Sci USA, vol.104, pp.2945-2949, 2007.

C. Y. Lee, J. P. Cantle, and X. W. Yang, Genetic manipulations of mutant huntingtin in mice: New insights into Huntington's disease pathogenesis, FEBS J, vol.280, pp.4382-4394, 2013.

A. M. Wojtowicz, A. Dvorzhak, M. Semtner, and R. Grantyn, Reduced tonic inhibition in striatal output neurons from Huntington mice due to loss of astrocytic GABA release through GAT-3, Front Neural Circuits, vol.7, p.188, 2013.

L. Wang, F. Lin, and J. Wang, Expression of mutant Nterminal huntingtin fragment (htt552-100Q) in astrocytes suppresses the secretion of BDNF, Brain Res, vol.1449, pp.69-82, 2012.

X. Tong, Y. Ao, and G. C. Faas, Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington's disease model mice, Nat Neurosci, vol.17, pp.694-703, 2014.

R. Jiang, B. Diaz-castro, L. L. Looger, and B. S. Khakh, Dysfunctional calcium and glutamate signaling in striatal astrocytes from Huntington's disease Model Mice, J Neurosci, vol.36, pp.3453-3470, 2016.

A. Benraiss, S. Wang, and S. Herrlinger, Human glia can both induce and rescue aspects of disease phenotype in Huntington disease, Nat Commun, vol.7, p.11758, 2016.

E. Chiu, I. R. Mackay, and P. B. Bhathal, Hepatic morphology in Huntington's chorea, J Neurol Neurosurg Psychiatry, vol.38, pp.1000-1002, 1975.

M. C. Chiang, H. M. Chen, and H. L. Lai, The A2A adenosine receptor rescues the urea cycle deficiency of Huntington's disease by enhancing the activity of the ubiquitin-proteasome system, Hum Mol Genet, vol.18, pp.2929-2942, 2009.

M. Björkqvist, E. J. Wild, and J. Thiele, A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease, J Exp Med, vol.205, pp.1869-1877, 2008.

A. Weiss, U. Träger, and E. J. Wild, Mutant huntingtin fragmentation in immune cells tracks Huntington's disease progression, J Clin Invest, vol.122, pp.3731-3736, 2012.

S. Ferré, L. F. Agnati, and F. Ciruela, Neurotransmitter receptor heteromers and their integrative role in ''local modules'': The striatal spine module, Brain Res Rev, vol.55, pp.55-67, 2007.

C. R. Gerfen and . Basal, The Rat Nervous System. Paxinos G, p.445508, 2004.

A. Araque, V. Parpura, R. P. Sanzgiri, and P. G. Haydon, Tripartite synapses: Glia, the unacknowledged partner, Trends Neurosci, vol.22, pp.208-215, 1999.

M. E. Rice, J. C. Patel, and S. J. Cragg, Dopamine release in the basal ganglia, Neuroscience, vol.198, pp.112-137, 2011.

O. Pascual, K. B. Casper, and C. Kubera, Astrocytic purinergic signaling coordinates synaptic networks, Science, vol.310, pp.113-116, 2005.

R. A. Cunha, How does adenosine control neuronal dysfunction and neurodegeneration?, J Neurochem, vol.139, pp.1019-1055, 2016.

F. Ciruela, V. Casadó, and R. J. Rodrigues, Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers, J Neurosci, vol.26, pp.2080-2087, 2006.

P. Popoli, P. Betto, R. Reggio, and G. Ricciarello, Adenosine A2A receptor stimulation enhances striatal extracellular glutamate levels in rats, Eur J Pharmacol, vol.287, pp.215-217, 1995.

M. Solinas, S. Ferré, Z. B. You, M. Karcz-kubicha, P. Popoli et al., Caffeine induces dopamine and glutamate release in the shell of the nucleus accumbens, J Neurosci, vol.22, pp.6321-6324, 2002.

J. Borycz, M. F. Pereira, and A. Melani, Differential glutamate-dependent and glutamate-independent adenosine A1 receptor-mediated modulation of dopamine release in different striatal compartments, J Neurochem, vol.101, pp.355-363, 2007.

C. Quiroz, R. Luján, and M. Uchigashima, Key modulatory role of presynaptic adenosine A2A receptors in cortical neurotransmission to the striatal direct pathway, ScientificWorldJournal, vol.9, pp.1321-1344, 2009.

C. Quiroz, M. Orrú, and W. Rea, Local Control of Extracellular Dopamine Levels in the Medial Nucleus Accumbens by a Glutamatergic Projection from the Infralimbic Cortex, J Neurosci, vol.36, pp.851-859, 2016.

A. L. Blum-et,

S. Cristóvão-ferreira, G. Navarro, and M. Brugarolas, A1R-A2AR heteromers coupled to Gs and G i/0 proteins modulate GABA transport into astrocytes. Purinergic Signal, vol.9, pp.433-449, 2013.

S. Ferré, B. B. Fredholm, M. Morelli, P. Popoli, and K. Fuxe, Adenosine-dopamin receptor-receptor interactions as an integrative mechanism in the basal ganglia, Trends Neurosci, vol.20, pp.482-487, 1997.

S. Ferre, O. Connor, W. T. Svenningsson, and P. , Dopamine D1 receptor-mediated facilitation of GABAergic neurotransmission in the rat strioentopenduncular pathway and its modulation by adenosine A1 receptormediated mechanisms, Eur J Neurosci, vol.8, pp.1545-1553, 1996.

P. Sokoloff, L. Foll, and B. , The dopamine D3 receptor, a quarter century later, Eur J Neurosci, vol.45, pp.2-19, 2017.

S. Ginés, J. Hillion, and M. Torvinen, Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes, Proc Natl Acad Sci USA, vol.97, pp.8606-8611, 2000.

J. Hillion, M. Canals, and M. Torvinen, Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors, J Biol Chem, vol.277, pp.18091-18097, 2002.

G. Navarro, A. Cordomí, and V. Casadó-anguera, Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase, Nat Commun, vol.9, p.1242, 2018.

S. Ferré, J. Bonaventura, and W. Zhu, Essential control of the function of the striatopallidal neuron by precoupled complexes of adenosine A2A-dopamine D2 receptor heterotetramers and adenylyl cyclase, Front Pharmacol, vol.9, p.243, 2018.

K. Alsene, J. Deckert, P. Sand, and H. De-wit, Association between A2a receptor gene polymorphisms and caffeineinduced anxiety, Neuropsychopharmacology, vol.28, pp.1694-1702, 2003.

E. Childs, C. Hohoff, J. Deckert, K. Xu, J. Badner et al., Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety, Neuropsychopharmacology, vol.33, pp.2791-2800, 2008.
DOI : 10.1038/npp.2008.17
URL : http://www.nature.com/npp/journal/v33/n12/pdf/npp200817a.pdf

P. J. Rogers, C. Hohoff, and S. V. Heatherley, Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption, Neuropsychopharmacology, vol.35, pp.1973-1983, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00542220

M. Shinohara, M. Saitoh, and D. Nishizawa, ADORA2A polymorphism predisposes children to encephalopathy with febrile status epilepticus, Neurology, vol.80, pp.1571-1576, 2013.
DOI : 10.1212/wnl.0b013e31828f18d8
URL : http://europepmc.org/articles/pmc3662331?pdf=render

C. M. Dhaenens, S. Burnouf, and C. Simonin, A genetic variation in the ADORA2A gene modifies age at onset in Huntington's disease, Neurobiol Dis, vol.35, pp.474-476, 2009.

E. Taherzadeh-fard, C. Saft, S. Wieczorek, J. T. Epplen, and L. Arning, Age at onset in Huntington's disease: Replication study on the associations of ADORA2A, HAP1 and OGG1, Neurogenetics, vol.11, pp.435-439, 2010.

C. Simonin, C. Duru, and J. Salleron, Association between caffeine intake and age at onset in Huntington's disease, Neurobiol Dis, vol.58, pp.179-182, 2013.
DOI : 10.1016/j.nbd.2013.05.013

M. Karcz-kubicha, K. Antoniou, and A. Terasmaa, Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration, Neuropsychopharmacology, vol.28, pp.1281-1291, 2003.

D. Blum, D. Gall, M. C. Galas, P. Alcantara, K. Bantubungi et al., The adenosine A1 receptor agonist adenosine amine congener exerts a neuroprotective effect against the development of striatal lesions and motor impairments in the 3-nitropropionic acid model of neurotoxicity, J Neurosci, vol.22, pp.9122-9133, 2002.

S. Mievis, D. Blum, and C. Ledent, A2A receptor knockout worsens survival and motor behaviour in a transgenic mouse model of Huntington's disease, Neurobiol Dis, vol.41, pp.570-576, 2011.

S. Y. Chou, Y. C. Lee, and H. M. Chen, CGS21680 attenuates symptoms of Huntington's disease in a transgenic mouse model, J Neurochem, vol.93, pp.310-320, 2005.

M. C. Cornelis, A. El-sohemy, and H. Campos, Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption, Am J Clin Nutr, vol.86, pp.240-244, 2007.
DOI : 10.1093/ajcn/86.1.240
URL : https://academic.oup.com/ajcn/article-pdf/86/1/240/23916684/znu00707000240.pdf

C. Coffee, . Genetics-consortium, M. C. Cornelis, and E. M. Byrne, Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption, Mol Psychiatry, vol.20, pp.647-656, 2015.

S. Paul, P. H. Elsinga, K. Ishiwata, R. A. Dierckx, and A. Van-waarde, Adenosine A(1) receptors in the central nervous system: Their functions in health and disease, and possible elucidation by PET imaging, Curr Med Chem, vol.18, pp.4820-4835, 2011.

D. K. Von-lubitz, J. M. Dambrosia, O. Kempski, and D. J. Redmond, Cyclohexyl adenosine protects against neuronal death following ischemia in the CA1 region of gerbil hippocampus, Stroke, vol.19, pp.1133-1139, 1988.

B. Zuchora, W. A. Turski, M. Wielosz, and E. M. Urban´skaurban´ska, Protective effect of adenosine receptor agonists in a new model of epilepsy-seizures evoked by mitochondrial toxin, 3-nitropropionic acid, in mice, Neurosci Lett, vol.305, pp.91-94, 2001.

P. D. Alfinito, S. P. Wang, L. Manzino, S. Rijhsinghani, G. D. Zeevalk et al., Adenosinergic protection of dopaminergic and GABAergic neurons against mitochondrial inhibition through receptors located in the substantia nigra and striatum, respectively, J Neurosci, vol.23, pp.10982-10987, 2003.

A. Bauer, K. Zilles, A. Matusch, C. Holzmann, O. Riess et al., Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington's disease mutation, J Neurochem, vol.94, pp.639-650, 2005.

A. Ferrante, A. Martire, and R. Pepponi, Expression, pharmacology and functional activity of adenosine A1 receptors in genetic models of Huntington's disease, Neurobiol Dis, vol.71, pp.193-204, 2014.

A. Matusch, C. Saft, and D. Elmenhorst, Cross sectional PET study of cerebral adenosine A 1 receptors in premanifest and manifest Huntington's disease, Eur J Nucl Med Mol Imaging, vol.41, pp.1210-1220, 2014.

M. I. Martinez-mir, A. Probst, and J. M. Palacios, Adenosine A2 receptors: Selective localization in the human basal ganglia and alterations with disease, Neuroscience, vol.42, pp.697-706, 1991.
DOI : 10.1016/0306-4522(91)90038-p

J. H. Cha, A. S. Frey, and S. A. Alsdorf, Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease, Philos Trans R Soc Lond B Biol Sci, vol.354, pp.981-989, 1999.

K. Ishiwata, N. Ogi, and N. Hayakawa, Adenosine A2A receptor imaging with [11C]KF18446 PET in the rat brain after quinolinic acid lesion: Comparison with the dopamine receptor imaging, Ann Nucl Med, vol.16, pp.467-475, 2002.

M. Orrú, J. M. Zanoveli, C. Quiroz, H. P. Nguyen, X. Guitart et al., Functional changes in postsynaptic adenosine A(2A) receptors during early stages of a rat model of Huntington disease, Exp Neurol, vol.232, pp.76-80, 2011.

E. Y. Chan, R. Luthi-carter, and A. Strand, Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease, Hum Mol Genet, vol.11, pp.1939-1951, 2002.

M. C. Chiang, Y. C. Lee, C. L. Huang, and Y. Chern, cAMPresponse element-binding protein contributes to suppression of the A2A adenosine receptor promoter by mutant Huntingtin with expanded polyglutamine residues, J Biol Chem, vol.280, pp.14331-14340, 2005.

A. Tarditi, A. Camurri, and K. Varani, Early and transient alteration of adenosine A2A receptor signaling in a mouse model of Huntington disease, Neurobiol Dis, vol.23, pp.44-53, 2006.

I. Villar-menéndez, M. Blanch, and S. Tyebji, Increased 5methylcytosine and decreased 5-hydroxymethylcytosine levels are associated with reduced striatal A2AR levels in Huntington's disease, Neuromolecular Med, vol.15, pp.295-309, 2013.

X. Guitart, J. Bonaventura, and W. Rea, Equilibrative nucleoside transporter ENT1 as a biomarker of Huntington disease, Neurobiol Dis, vol.96, pp.47-53, 2016.

J. S. Steffan, A. Kazantsev, and O. Spasic-boskovic, The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription, Proc Natl Acad Sci USA, vol.97, pp.6763-6768, 2000.

F. C. Nucifora, M. Sasaki, and M. F. Peters, Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity, Science, vol.291, pp.2423-2428, 2001.

A. W. Dunah, H. Jeong, and A. Griffin, Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease, Science, vol.296, pp.2238-2243, 2002.

S. H. Li, A. L. Cheng, and H. Zhou, Interaction of Huntington disease protein with transcriptional activator Sp1, Mol Cell Biol, vol.22, pp.1277-1287, 2002.

J. H. Cha, C. M. Kosinski, and J. A. Kerner, Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene, Proc Natl Acad Sci USA, vol.95, pp.6480-6485, 1998.

S. P. Buira, G. Dentesano, and J. L. Albasanz, DNA methylation and Yin Yang-1 repress adenosine A2A receptor levels in human brain, J Neurochem, vol.115, pp.283-295, 2010.

L. Mangiarini, K. Sathasivam, and M. Seller, Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice, Cell, vol.87, pp.493-506, 1996.

J. P. Vonsattel, Huntington disease models and human neuropathology: Similarities and differences, Acta Neuropathol, vol.115, pp.55-69, 2008.

K. Varani, D. Rigamonti, and S. Sipione, Aberrant amplification of A(2A) receptor signaling in striatal cells expressing mutant huntingtin, FASEB J, vol.15, pp.1245-1247, 2001.

K. Varani, A. C. Bachoud-lévi, and C. Mariotti, Biological abnormalities of peripheral A(2A) receptors in a large representation of polyglutamine disorders and Huntington's disease stages, Neurobiol Dis, vol.27, pp.36-43, 2007.

V. Maglione, M. Cannella, T. Martino, D. Blasi, A. Frati et al., The platelet maximum number of A2Areceptor binding sites (Bmax) linearly correlates with age at onset and CAG repeat expansion in Huntington's disease patients with predominant chorea, Neurosci Lett, vol.393, pp.27-30, 2006.

A. A. Roussakis and P. Piccini, PET Imaging in Huntington's Disease, J Huntingtons Dis, vol.4, pp.287-296, 2015.

A. Bauer, M. H. Holschbach, and P. T. Meyer, In vivo imaging of adenosine A1 receptors in the human brain with [18F]CPFPX and positron emission tomography, Neuroimage, vol.19, pp.1760-1769, 2003.

M. H. Holschbach, R. A. Olsson, and D. Bier, Synthesis and evaluation of no-carrier-added 8-cyclopentyl-3-(3[(18)F]fluoropropyl)-1-propylxanthine ([(18)F]CPFPX): A potent and selective A(1)-adenosine receptor antagonist for in vivo imaging, J Med Chem, vol.45, pp.5150-5156, 2002.

P. T. Meyer, D. Elmenhorst, and C. Boy, Effect of aging on cerebral A1 adenosine receptors: A [18F]CPFPX PET study in humans, Neurobiol Aging, vol.28, pp.1914-1924, 2007.

S. Khanapur, W. Av, K. Ishiwata, K. L. Leenders, R. A. Dierckx et al., Adenosine A(2A) receptor antagonists as positron emission tomography (PET) tracers, Curr Med Chem, vol.21, pp.312-328, 2014.

A. Van-waarde, R. Dierckx, and X. Zhou, Potential therapeutic applications of adenosine A(2A) receptor ligands and opportunities for A(2A) receptor imaging, Med Res Rev, vol.38, pp.5-56, 2018.

R. M. Moresco, S. Todde, and S. Belloli, In vivo imaging of adenosine A2A receptors in rat and primate brain using [11C]SCH442416, Eur J Nucl Med Mol Imaging, vol.32, pp.405-413, 2005.

X. Zhou, R. Boellaard, and K. Ishiwata, In Vivo Evaluation of (11)C-preladenant for PET imaging of adenosine A(2A) receptors in the conscious monkey, J Nucl Med, vol.58, pp.762-767, 2017.

X. Zhou, S. Khanapur, D. Jong, and J. R. , In vivo evaluation of [(11)C]preladenant positron emission tomography for quantification of adenosine A(2A) receptors in the rat brain, J Cereb Blood Flow Metab, vol.37, pp.577-589, 2017.

M. Sakata, K. Ishibashi, and M. Imai, Initial evaluation of an adenosine A(2A) receptor ligand, (11)C-preladenant, in healthy human subjects, J Nucl Med, vol.58, pp.1464-1470, 2017.

S. Von-hörsten, I. Schmitt, and H. P. Nguyen, Transgenic rat model of Huntington's disease, Hum Mol Genet, vol.12, pp.617-624, 2003.

M. Orrú, J. Bake?ová, and M. Brugarolas, Striatal preand postsynaptic profile of adenosine A(2A) receptor antagonists, PLoS One, vol.6, p.16088, 2011.

A. L. Blum-et,

L. B. Menalled, A. E. Kudwa, and S. Miller, Comprehensive behavioral and molecular characterization of a new knock-in mouse model of Huntington's disease: zQ175, PLoS One, vol.7, p.49838, 2012.

D. Boison, J. F. Chen, and B. B. Fredholm, Adenosine signaling and function in glial cells, Cell Death Differ, vol.17, pp.1071-1082, 2010.

F. E. Parkinson, V. L. Damaraju, and K. Graham, Molecular biology of nucleoside transporters and their distributions and functions in the brain, Curr Top Med Chem, vol.11, pp.948-972, 2011.

C. G. Dulla and S. A. Masino, Physiology and metabolic regulation of adenosine: Mechanisms, Adenosine. A Key Link Between Metabolism and Brain Activity

L. Alanko, T. Porkka-heiskanen, and S. Soinila, Localization of equilibrative nucleoside transporters in the rat brain, J Chem Neuroanat, vol.31, pp.162-168, 2006.

A. Bicket, P. Mehrabi, and Z. Naydenova, Novel regulation of equlibrative nucleoside transporter 1 (ENT1) by receptor-stimulated Ca2+-dependent calmodulin binding, Am J Physiol Cell Physiol, vol.310, pp.808-820, 2016.

Y. H. Kao, M. S. Lin, and C. M. Chen, Targeting ENT1 and adenosine tone for the treatment of Huntington's disease, Hum Mol Genet, vol.26, pp.467-478, 2017.

T. A. Alston, L. Mela, and H. J. Bright, 3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase, Proc Natl Acad Sci, pp.74-3767, 1977.

E. Brouillet, B. G. Jenkins, and B. T. Hyman, Agedependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid, J Neurochem, vol.60, pp.356-359, 1993.

K. A. Jacobson, R. Balasubramanian, F. Deflorian, and Z. G. Gao, G protein-coupled adenosine (P1) and P2Y receptors: Ligand design and receptor interactions, Purinergic Signal, vol.8, pp.419-436, 2012.

D. A. Shear, J. Dong, C. D. Gundy, K. L. Haik-creguer, and G. L. Dunbar, Comparison of intrastriatal injections of quinolinic acid and 3-nitropropionic acid for use in animal models of Huntington's disease, Prog Neuropsychopharmacol Biol Psychiatry, vol.22, pp.1217-1240, 1998.

O. A. Andreassen, R. J. Ferrante, and D. B. Hughes, Malonate and 3-nitropropionic acid neurotoxicity are reduced in transgenic mice expressing a caspase-1 dominant-negative mutant, J Neurochem, vol.75, pp.847-852, 2000.

M. F. Beal, E. Brouillet, B. Jenkins, R. Henshaw, B. Rosen et al., Age-dependent striatal excitotoxic lesions produced by the endogenous mitochondrial inhibitor malonate, J Neurochem, vol.61, pp.1147-1150, 1993.

C. A. Messam, J. G. Greene, J. T. Greenamyre, and M. B. Robinson, Intrastriatal injections of the succinate dehydrogenase inhibitor, malonate, cause a rise in extracellular amino acids that is blocked by MK-801, Brain Res, vol.684, pp.221-224, 1995.

J. S. Fink, A. Kalda, and H. Ryu, Genetic and pharmacological inactivation of the adenosine A2A receptor attenuates 3-nitropropionic acid-induced striatal damage, J Neurochem, vol.88, pp.538-544, 2004.

M. Galluzzo, A. Pintor, A. Pezzola, R. Grieco, F. Borsini et al., Behavioural and neurochemical characterization of the adenosine A2A receptor antagonist ST1535, Eur J Pharmacol, vol.579, pp.149-152, 2008.

R. Reggio, A. Pezzola, and P. Popoli, The intrastratial injection of an adenosine A(2) receptor antagonist prevents frontal cortex EEG abnormalities in a rat model of Huntington's disease, Brain Res, vol.831, pp.315-318, 1999.

M. L. Scattoni, A. Valanzano, and A. Pezzola, Adenosine A2A receptor blockade before striatal excitotoxic lesions prevents long term behavioural disturbances in the quinolinic rat model of Huntington's disease, Behav Brain Res, vol.176, pp.216-221, 2007.

M. T. Tebano, A. Pintor, and C. Frank, Adenosine A2A receptor blockade differentially influences excitotoxic mechanisms at pre-and postsynaptic sites in the rat striatum, J Neurosci Res, vol.77, pp.100-107, 2004.

Q. Y. Huang, C. Wei, and L. Yu, Adenosine A2A receptors in bone marrow-derived cells but not in forebrain neurons are important contributors to 3-nitropropionic acid-induced striatal damage as revealed by cell-typeselective inactivation, J Neurosci, vol.26, pp.11371-11378, 2006.

D. Blum, R. Hourez, M. C. Galas, P. Popoli, and S. N. Schiffmann, Adenosine receptors and Huntington's disease: Implications for pathogenesis and therapeutics, Lancet Neurol, vol.2, pp.366-374, 2003.

M. A. Pouladi, A. Morton, and M. R. Hayden, Choosing an animal model for the study of Huntington's disease, Nat Rev Neurosci, vol.14, pp.708-721, 2013.

R. J. Ferrante, Mouse models of Huntington's disease and methodological considerations for therapeutic trials, Biochim Biophys Acta, vol.1792, pp.506-520, 2009.

J. Y. Li, N. Popovic, and P. Brundin, The use of the R6 transgenic mouse models of Huntington's disease in attempts to develop novel therapeutic strategies, NeuroRx, vol.2, pp.447-464, 2005.

L. B. Menalled, Knock-in mouse models of Huntington's disease, NeuroRx, vol.2, pp.465-470, 2005.

L. B. Menalled and M. F. Chesselet, Mouse models of Huntington's disease, Trends Pharmacol Sci, vol.23, pp.32-39, 2002.

R. Luthi-carter, A. Strand, and N. L. Peters, Decreased expression of striatal signaling genes in a mouse model of Huntington's disease, Hum Mol Genet, vol.9, pp.1259-1271, 2000.

C. Cepeda, D. M. Cummings, and M. A. Hickey, Rescuing the corticostriatal synaptic disconnection in the R6/2 mouse model of Huntington's disease: Exercise, adenosine receptors and ampakines, PLoS Curr, vol.2, p.1182, 2010.

N. K. Huang, J. H. Lin, and J. T. Lin, A new drug design targeting the adenosinergic system for Huntington's disease, PLoS One, vol.6, p.20934, 2011.

R. L. Potenza, M. T. Tebano, and A. Martire, Adenosine A(2A) receptors modulate BDNF both in normal conditions and in experimental models of Huntington's disease, Purinergic Signal, vol.3, pp.333-338, 2007.

A. Martire, R. Pepponi, M. R. Domenici, A. Ferrante, V. Chiodi et al., BDNF prevents NMDA-induced toxicity in models of Huntington's disease: The effects are genotype specific and adenosine A2A receptor is involved, J Neurochem, vol.125, pp.225-235, 2013.

M. R. Domenici, M. L. Scattoni, and A. Martire, Behavioral and electrophysiological effects of the adenosine A2A receptor antagonist SCH 58261 in R6/2 Huntington's disease mice, Neurobiol Dis, vol.28, pp.197-205, 2007.

M. Gianfriddo, A. Melani, D. Turchi, M. G. Giovannini, and F. Pedata, Adenosine and glutamate extracellular concentrations and mitogen-activated protein kinases in the striatum of Huntington transgenic mice. Selective antagonism of adenosine A2A receptors reduces transmitter outflow, Neurobiol Dis, vol.17, pp.77-88, 2004.

S. Cipriani, E. Bizzoco, M. Gianfriddo, A. Melani, M. G. Vannucchi et al., Adenosine A2A receptor antagonism increases nNOS-immunoreactive neurons in the striatum of Huntington transgenic mice, Exp Neurol, vol.13, pp.163-170, 2008.

W. Li, H. B. Silva, and J. Real, Inactivation of adenosine A2A receptors reverses working memory deficits at early stages of Huntington's disease models, Neurobiol Dis, vol.79, pp.70-80, 2015.

S. Tyebji, A. Saavedra, and P. M. Canas, Hyperactivation of D1 and A2A receptors contributes to cognitive dysfunction in Huntington's disease, Neurobiol Dis, vol.74, pp.41-57, 2015.

J. B. Chen, E. M. Liu, and T. R. Chern, Design and synthesis of novel dual-action compounds targeting the adenosine A(2A) receptor and adenosine transporter for neuroprotection, ChemMedChem, vol.6, pp.1390-1400, 2011.

C. H. Lin, S. Tallaksen-greene, and W. M. Chien, Neurological abnormalities in a knock-in mouse model of Huntington's disease, Hum Mol Genet, vol.10, pp.137-144, 2001.

X. Guitart, Y. Chern, and S. Ferré, Targeting the equilibrative nucleoside transporter ENT1 in Huntington disease, Oncotarget, vol.8, pp.12550-12551, 2017.

S. Ferré, M. Herrera-marschitz, M. Grabowska-andén, U. Ungerstedt, M. Casas et al., Postsynaptic dopamine/adenosine interaction: I. Adenosine analogues inhibit dopamine D2-mediated behaviour in short-term reserpinized mice, Eur J Pharmacol, vol.192, pp.25-30, 1991.

S. Ferré, P. Popoli, and L. Giménez-llort, Postsynaptic antagonistic interaction between adenosine A1 and dopamine D1 receptors, Neuroreport, vol.6, pp.73-76, 1994.

S. Ferré, C. Quiroz, and X. Guitart, Pivotal role of adenosine neurotransmission in restless legs syndrome, Front Neurosci, vol.11, p.722, 2018.