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Journal of Neural Transmission

, Volume 125, Issue 3, pp 325–335 | Cite as

The use of nonhuman primate models to understand processes in Parkinson’s disease

  • Javier Blesa
  • Inés Trigo-Damas
  • Natalia López-González del Rey
  • José A. Obeso
Translational Neurosciences - Review Article

Abstract

Research with animal models has led to critical health advances that have saved or improved the lives of millions of human beings. Specifically, nonhuman primate’s genetic and anatomo-physiological similarities to humans are especially important for understanding processes like Parkinson’s disease, which only occur in humans. Unambiguously, the unique contribution made by nonhuman primate research to our understanding of Parkinson’s disease is widely recognized. For example, monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonisms are responsive to dopamine replacement therapies, mimicking what is seen in PD patients. Moreover, groundbreaking neuroanatomical and electrophysiological studies using this monkey model in the 1980s and 1990s enabled researchers to identify the neuronal circuits responsible for the cardinal motor features of PD. This led to the development of subthalamic surgical ablation and deep brain stimulation, the current therapeutic gold standard for neurosurgical treatment. More recently, the mechanisms of α-synuclein spreading testing the prion hypothesis for PD have yielded exciting results. In this review, we discuss and highlight how the findings from nonhuman primate research contribute to our understanding of idiopathic Parkinson’s disease.

Keywords

Animal models Nonhuman primates Parkinson’s disease MPTP DBS 

References

  1. Aarsland D, Kramberger MG (2015) Neuropsychiatric symptoms in Parkinson’s disease. J Parkinsons Dis 5:659–667. doi: 10.3233/JPD-150604 PubMedCrossRefGoogle Scholar
  2. Adachi K, Kobayashi M, Kawasaki T et al (2012) Disruption of programmed masticatory movements in unilateral MPTP-treated monkeys as a model of jaw movement abnormality in Parkinson’s disease. J Neural Transm 119:933–941. doi: 10.1007/s00702-012-0768-0 PubMedCrossRefGoogle Scholar
  3. Ai Y, Markesbery W, Zhang Z et al (2003) Intraputamenal infusion of GDNF in aged rhesus monkeys: distribution and dopaminergic effects. J Comp Neurol 461:250–261. doi: 10.1002/cne.10689 PubMedCrossRefGoogle Scholar
  4. Akai T, Ozawa M, Yamaguchi M et al (1995) Behavioral involvement of central dopamine D1 and D2 receptors in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys. Jpn J Pharmacol 67:117–124PubMedCrossRefGoogle Scholar
  5. Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12:366–375PubMedCrossRefGoogle Scholar
  6. Almirall H, Pigarev I, de la Calzada MD et al (1999) Nocturnal sleep structure and temperature slope in MPTP treated monkeys. J Neural Transm 106:1125–1134. doi: 10.1007/s007020050228 PubMedCrossRefGoogle Scholar
  7. Aziz TZ, Peggs D, Sambrook MA, Crossman AR (1991) Lesion of the subthalamic nucleus for the alleviation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the primate. Mov Disord 6:288–292PubMedCrossRefGoogle Scholar
  8. Balestrino R, Martinez-Martin P (2017) Neuropsychiatric symptoms, behavioural disorders, and quality of life in Parkinson’s disease. J Neurol Sci 373:173–178. doi: 10.1016/j.jns.2016.12.060 PubMedCrossRefGoogle Scholar
  9. Ballanger B, Beaudoin-Gobert M, Neumane S et al (2016) Imaging dopamine and serotonin systems on MPTP monkeys: a longitudinal PET investigation of compensatory mechanisms. J Neurosci 36:1577–1589. doi: 10.1523/JNEUROSCI.2010-15.2016 PubMedCrossRefGoogle Scholar
  10. Ballard PA, Tetrud JW, Langston JW (1985) Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): seven cases. Neurology 35:949–956PubMedCrossRefGoogle Scholar
  11. Bankiewicz KS, Eberling JL, Kohutnicka M et al (2000) Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. Exp Neurol 164:2–14. doi: 10.1006/exnr.2000.7408 PubMedCrossRefGoogle Scholar
  12. Bankiewicz KS, Forsayeth J, Eberling JL et al (2006) Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC. Mol Ther 14:564–570. doi: 10.1016/j.ymthe.2006.05.005 PubMedCrossRefGoogle Scholar
  13. Bannon D, Landau AM, Doudet DJ (2015) How relevant are imaging findings in animal models of movement disorders to human disease? Curr Neurol Neurosci Rep 15:53. doi: 10.1007/s11910-015-0571-z PubMedCrossRefGoogle Scholar
  14. Barraud Q, Lambrecq V, Forni C et al (2009) Sleep disorders in Parkinson’s disease: the contribution of the MPTP non-human primate model. Exp Neurol 219:574–582. doi: 10.1016/j.expneurol.2009.07.019 PubMedCrossRefGoogle Scholar
  15. Belaid H, Adrien J, Laffrat E et al (2014) Sleep disorders in Parkinsonian macaques: effects of l-Dopa treatment and pedunculopontine nucleus lesion. J Neurosci 34:9124–9133. doi: 10.1523/JNEUROSCI.0181-14.2014 PubMedPubMedCentralCrossRefGoogle Scholar
  16. Benazzouz A, Gross C, Féger J et al (1993) Reversal of rigidity and improvement in motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys. Eur J Neurosci 5:382–389PubMedCrossRefGoogle Scholar
  17. Berger B, Gaspar P, Verney C (1991) Dopaminergic innervation of the cerebral cortex: unexpected differences between rodents and primates. Trends Neurosci 14:21–27PubMedCrossRefGoogle Scholar
  18. Bergman H, Wichmann T, DeLong MR (1990) Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science (80) 249:1436–1438Google Scholar
  19. Bergman H, Wichmann T, Karmon B, DeLong MR (1994) The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol 72:507–520PubMedCrossRefGoogle Scholar
  20. Bezard E, Tronci E, Pioli EY et al (2013) Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia. Mov Disord 28:1088–1096. doi: 10.1002/mds.25366 PubMedCrossRefGoogle Scholar
  21. Bezard E, Pioli EY, Li Q et al (2014) The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model. Mov Disord 29:1074–1079. doi: 10.1002/mds.25920 PubMedCrossRefGoogle Scholar
  22. Blanchet PJ, Konitsiotis S, Chase TN (1998) Amantadine reduces levodopa-induced dyskinesias in parkinsonian monkeys. Mov Disord 13:798–802. doi: 10.1002/mds.870130507 PubMedCrossRefGoogle Scholar
  23. Blesa J, Przedborski S (2014) Parkinson’s disease: animal models and dopaminergic cell vulnerability. Front Neuroanat 8:155. doi: 10.3389/fnana.2014.00155 PubMedPubMedCentralCrossRefGoogle Scholar
  24. Blesa J, Juri C, Collantes M et al (2010) Progression of dopaminergic depletion in a model of MPTP-induced Parkinsonism in non-human primates. An (18)F-DOPA and (11)C-DTBZ PET study. Neurobiol Dis 38:456–463. doi: 10.1016/j.nbd.2010.03.006 PubMedCrossRefGoogle Scholar
  25. Blesa J, Pifl C, Sánchez-González MA et al (2012) The nigrostriatal system in the presymptomatic and symptomatic stages in the MPTP monkey model: a PET, histological and biochemical study. Neurobiol Dis 48:79–91. doi: 10.1016/j.nbd.2012.05.018 PubMedCrossRefGoogle Scholar
  26. Boyce S, Rupniak NM, Steventon MJ, Iversen SD (1990) Nigrostriatal damage is required for induction of dyskinesias by l-DOPA in squirrel monkeys. Clin Neuropharmacol 13:448–458PubMedCrossRefGoogle Scholar
  27. Braak H, Del Tredici K, Rüb U et al (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211PubMedCrossRefGoogle Scholar
  28. Brichta L, Greengard P, Flajolet M (2013) Advances in the pharmacological treatment of Parkinson’s disease: targeting neurotransmitter systems. Trends Neurosci 36:543–554. doi: 10.1016/j.tins.2013.06.003 PubMedCrossRefGoogle Scholar
  29. Brooks WJ, Jarvis MF, Wagner GC (1989) Astrocytes as a primary locus for the conversion MPTP into MPP+. J Neural Transm 76:1–12. doi: 10.1007/BF01244987 PubMedCrossRefGoogle Scholar
  30. Burns RS, Chiueh CC, Markey SP et al (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 80:4546–4550PubMedPubMedCentralCrossRefGoogle Scholar
  31. Canron M-H, Perret M, Vital A et al (2012) Age-dependent α-synuclein aggregation in the Microcebus murinus lemur primate. Sci Rep 2:910. doi: 10.1038/srep00910 PubMedPubMedCentralCrossRefGoogle Scholar
  32. Carpenter MB, Whittier JR, Mettler FA (1950) Analysis of choreoid hyperkinesia in the Rhesus monkey; surgical and pharmacological analysis of hyperkinesia resulting from lesions in the subthalamic nucleus of Luys. J Comp Neurol 92:293–331PubMedCrossRefGoogle Scholar
  33. Chaumette T, Lebouvier T, Aubert P et al (2009) Neurochemical plasticity in the enteric nervous system of a primate animal model of experimental Parkinsonism. Neurogastroenterol Motil 21:215–222PubMedCrossRefGoogle Scholar
  34. Chen JJ (2010) Parkinson’s disease: health-related quality of life, economic cost, and implications of early treatment. Am J Manag Care 16:S87–S93Google Scholar
  35. Chen M, Liu J, Lu Y et al (2016) Age-dependent alpha-synuclein accumulation is correlated with elevation of mitochondrial TRPC3 in the brains of monkeys and mice. J Neural Transm. doi: 10.1007/s00702-016-1654-y Google Scholar
  36. Chu Y, Kordower JH (2007) Age-associated increases of α-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: is this the target for Parkinson’s disease? Neurobiol Dis 25:134–149. doi: 10.1016/j.nbd.2006.08.021 PubMedCrossRefGoogle Scholar
  37. Collier TJ, Lipton J, Daley BF et al (2007) Aging-related changes in the nigrostriatal dopamine system and the response to MPTP in nonhuman primates: diminished compensatory mechanisms as a prelude to parkinsonism. Neurobiol Dis 26:56–65. doi: 10.1016/j.nbd.2006.11.013 PubMedPubMedCentralCrossRefGoogle Scholar
  38. Coune PG, Schneider BL, Aebischer P (2012) Parkinson’s disease: gene therapies. Cold Spring Harb Perspect Med 2:a009431–a009432. doi: 10.1101/cshperspect.a009431 PubMedPubMedCentralCrossRefGoogle Scholar
  39. Crossman AR, Mitchell IJ, Sambrook MA (1985) Regional brain uptake of 2-deoxyglucose in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the macaque monkey. Neuropharmacology 24:587–591PubMedCrossRefGoogle Scholar
  40. de Celis Alonso B, Hidalgo-Tobón SS, Menéndez-González M et al (2015) Magnetic resonance techniques applied to the diagnosis and treatment of Parkinson’s disease. Front Neurol 6:146. doi: 10.3389/fneur.2015.00146 Google Scholar
  41. DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281–285PubMedCrossRefGoogle Scholar
  42. DeLong MR, Crutcher MD, Georgopoulos AP (1985) Primate globus pallidus and subthalamic nucleus: functional organization. J Neurophysiol 53:530–543PubMedCrossRefGoogle Scholar
  43. Deuschl G, Schade-Brittinger C, Krack P et al (2006) A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med 355:896–908. doi: 10.1056/NEJMoa060281 PubMedCrossRefGoogle Scholar
  44. Di Paolo T, Grégoire L, Feuerbach D et al (2014) AQW051, a novel and selective nicotinic acetylcholine receptor α7 partial agonist, reduces l-Dopa-induced dyskinesias and extends the duration of l-Dopa effects in parkinsonian monkeys. Parkinsonism Relat Disord 20:1119–1123. doi: 10.1016/j.parkreldis.2014.05.007 PubMedCrossRefGoogle Scholar
  45. Didier ES, MacLean AG, Mohan M et al (2016) Contributions of nonhuman primates to research on aging. Vet Pathol 53:277–290. doi: 10.1177/0300985815622974 PubMedPubMedCentralCrossRefGoogle Scholar
  46. Downs ME, Buch A, Karakatsani ME et al (2015) Blood–brain barrier opening in behaving non-human primates via focused ultrasound with systemically administered microbubbles. Sci Rep 5:15076. doi: 10.1038/srep15076 PubMedPubMedCentralCrossRefGoogle Scholar
  47. Du G, Lewis MM, Styner M et al (2011) Combined R2* and diffusion tensor imaging changes in the substantia nigra in Parkinson’s disease. Mov Disord 26:1627–1632. doi: 10.1002/mds.23643 PubMedPubMedCentralCrossRefGoogle Scholar
  48. Everett GM, Blockus LE, Shepperd IM (1956) Tremor induced by tremorine and its antagonism by anti-Parkinson drugs. Science 124:79PubMedCrossRefGoogle Scholar
  49. Falkenburger BH, Saridaki T, Dinter E (2016) Cellular models for Parkinson’s disease. J Neurochem 139:121–130. doi: 10.1111/jnc.13618 PubMedCrossRefGoogle Scholar
  50. Feigin A, Kaplitt MG, Tang C et al (2007) Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson’s disease. Proc Natl Acad Sci 104:19559–19564. doi: 10.1073/pnas.0706006104 PubMedPubMedCentralCrossRefGoogle Scholar
  51. Fox SH, Brotchie JM (2010) The MPTP-lesioned non-human primate models of Parkinson’s disease. Past, present, and future. Prog Brain Res 184:133–157. doi: 10.1016/S0079-6123(10)84007-5 PubMedCrossRefGoogle Scholar
  52. Fox SH, Visanji NP, Johnston TH et al (2006) Dopamine receptor agonists and levodopa and inducing psychosis-like behavior in the MPTP primate model of Parkinson disease. Arch Neurol 63:1343–1344. doi: 10.1001/archneur.63.9.1343 PubMedCrossRefGoogle Scholar
  53. Fox SH, Visanji N, Reyes G et al (2010) Neuropsychiatric behaviors in the MPTP marmoset model of Parkinson’s disease. Can J Neurol Sci 37:86–95PubMedCrossRefGoogle Scholar
  54. George S, Brundin P (2017) Solving the conundrum of insoluble protein aggregates. Lancet Neurol 16(4):258–259. doi: 10.1016/S1474-4422(17)30045-5
  55. Gill SS, Patel NK, Hotton GR et al (2003) Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med 9:589–595. doi: 10.1038/nm850 PubMedCrossRefGoogle Scholar
  56. Goedert M, Masuda-Suzukake M, Falcon B (2016) Like prions: the propagation of aggregated tau and α-synuclein in neurodegeneration. Brain. doi: 10.1093/brain/aww230 PubMedGoogle Scholar
  57. Grégoire L, Morin N, Ouattara B et al (2011) The acute antiparkinsonian and antidyskinetic effect of AFQ056, a novel metabotropic glutamate receptor type 5 antagonist, in l-Dopa-treated parkinsonian monkeys. Parkinsonism Relat Disord 17:270–276. doi: 10.1016/j.parkreldis.2011.01.008 PubMedCrossRefGoogle Scholar
  58. Grondin R, Zhang Z, Yi A et al (2002) Chronic, controlled GDNF infusion promotes structural and functional recovery in advanced parkinsonian monkeys. Brain 125:2191–2201PubMedCrossRefGoogle Scholar
  59. Grondin R, Cass WA, Zhang Z et al (2003) Glial cell line-derived neurotrophic factor increases stimulus-evoked dopamine release and motor speed in aged rhesus monkeys. J Neurosci 23:1974–1980PubMedGoogle Scholar
  60. Gubellini P, Kachidian P (2015) Animal models of Parkinson’s disease: an updated overview. Rev Neurol (Paris) 171:750–761. doi: 10.1016/j.neurol.2015.07.011 CrossRefGoogle Scholar
  61. Guridi J, Rodriguez-Oroz MC, Lozano AM, Moro E, Albanese A, Nuttin B, Gybels J, Ramos E, Obeso JA (2000) Targeting the basal ganglia for deep brain stimulation in Parkinson's disease. Neurology 55(6):S21–S28Google Scholar
  62. Guridi J, Marigil M, Becerra V, Parras O (2016) Neuroprotective subthalamotomy in Parkinson’s disease. The role of magnetic resonance-guided focused ultrasound in early surgery. Neurocirugia (Astur) 27:285–290. doi: 10.1016/j.neucir.2016.02.006 CrossRefGoogle Scholar
  63. Hacia JG, Makalowski W, Edgemon K et al (1998) Evolutionary sequence comparisons using high-density oligonucleotide arrays. Nat Genet 18:155–158. doi: 10.1038/ng0298-155 PubMedCrossRefGoogle Scholar
  64. Hikishima K, Ando K, Komaki Y et al (2015a) Voxel-based morphometry of the marmoset brain: in vivo detection of volume loss in the substantia nigra of the MPTP-treated Parkinson’s disease model. Neuroscience 300:585–592. doi: 10.1016/j.neuroscience.2015.05.041 PubMedCrossRefGoogle Scholar
  65. Hikishima K, Ando K, Yano R et al (2015b) Parkinson disease: diffusion MR imaging to detect nigrostriatal pathway loss in a marmoset model treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Radiology 275:430–437. doi: 10.1148/radiol.14140601 PubMedCrossRefGoogle Scholar
  66. Hill MP, Ravenscroft P, Bezard E et al (2004) Levetiracetam potentiates the antidyskinetic action of amantadine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of Parkinson’s disease. J Pharmacol Exp Ther 310:386–394. doi: 10.1124/jpet.104.066191 PubMedCrossRefGoogle Scholar
  67. Huot P, Johnston TH, Fox SH et al (2015) The highly-selective 5-HT1A agonist F15599 reduces l-DOPA-induced dyskinesia without compromising anti-parkinsonian benefits in the MPTP-lesioned macaque. Neuropharmacology 97:306–311. doi: 10.1016/j.neuropharm.2015.05.033 PubMedCrossRefGoogle Scholar
  68. Hyacinthe C, Barraud Q, Tison F et al (2014) D1 receptor agonist improves sleep-wake parameters in experimental parkinsonism. Neurobiol Dis 63:20–24. doi: 10.1016/j.nbd.2013.10.029 PubMedCrossRefGoogle Scholar
  69. Iranzo A (2016) Sleep in neurodegenerative diseases. Sleep Med Clin 11:1–18. doi: 10.1016/j.jsmc.2015.10.011 PubMedCrossRefGoogle Scholar
  70. Jackson MJ, Swart T, Pearce RKB, Jenner P (2014) Cholinergic manipulation of motor disability and l-DOPA-induced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets. J Neural Transm 121:163–169. doi: 10.1007/s00702-013-1082-1 PubMedCrossRefGoogle Scholar
  71. Jarraya B, Boulet S, Scott Ralph G et al (2009) Dopamine gene therapy for Parkinson’s disease in a nonhuman primate without associated dyskinesia. Sci Transl Med 1:2ra4–2ra4. doi: 10.1126/scitranslmed.3000130
  72. Javitch JA, D’Amato RJ, Strittmatter SM, Snyder SH (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci USA 82:2173–2177PubMedPubMedCentralCrossRefGoogle Scholar
  73. Jellinger KA (2015) Neuropathobiology of non-motor symptoms in Parkinson disease. J Neural Transm 122:1429–1440. doi: 10.1007/s00702-015-1405-5 PubMedCrossRefGoogle Scholar
  74. Jenner P, Rupniak NM, Rose S et al (1984) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the common marmoset. Neurosci Lett 50:85–90PubMedCrossRefGoogle Scholar
  75. Joel D, Weiner I (2000) The connections of the dopaminergic system with the striatum in rats and primates: an analysis with respect to the functional and compartmental organization of the striatum. Neuroscience 96:451–474PubMedCrossRefGoogle Scholar
  76. Johnston TM, Fox SH (2014) Symptomatic models of Parkinson’s disease and l-DOPA-induced dyskinesia in non-human primates. In: Current topics in behavioral neurosciences, pp 221–235Google Scholar
  77. Johnston LC, Eberling J, Pivirotto P et al (2009) Clinically relevant effects of convection-enhanced delivery of AAV2-GDNF on the dopaminergic nigrostriatal pathway in aged rhesus monkeys. Hum Gene Ther 20:497–510. doi: 10.1089/hum.2008.137 PubMedPubMedCentralCrossRefGoogle Scholar
  78. Johnston TH, Huot P, Fox SH et al (2013) TC-8831, a nicotinic acetylcholine receptor agonist, reduces l-DOPA-induced dyskinesia in the MPTP macaque. Neuropharmacology 73:337–347. doi: 10.1016/j.neuropharm.2013.06.005 PubMedCrossRefGoogle Scholar
  79. Kalia LV, Lang AE (2015) Parkinson’s disease. Lancet 386:896–912. doi: 10.1016/S0140-6736(14)61393-3 PubMedCrossRefGoogle Scholar
  80. Kaplitt MG, Feigin A, Tang C et al (2007) Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial. Lancet 369:2097–2105. doi: 10.1016/S0140-6736(07)60982-9 PubMedCrossRefGoogle Scholar
  81. Karachi C, Francois C (2017) Role of the pedunculopontine nucleus in controlling gait and sleep in normal and parkinsonian monkeys. J Neural Transm. doi: 10.1007/s00702-017-1678-y PubMedGoogle Scholar
  82. Kimura K, Inoue K, Kuroiwa Y et al (2016) Propagated but topologically distributed forebrain neurons expressing alpha-synuclein in aged macaques. PLoS One 11:e0166861. doi: 10.1371/journal.pone.0166861 PubMedPubMedCentralCrossRefGoogle Scholar
  83. Kirik D, Annett LE, Burger C et al (2003) Nigrostriatal alpha-synucleinopathy induced by viral vector-mediated overexpression of human alpha-synuclein: a new primate model of Parkinson’s disease. Proc Natl Acad Sci USA 100:2884–2889. doi: 10.1073/pnas.0536383100 PubMedPubMedCentralCrossRefGoogle Scholar
  84. Ko WKD, Pioli E, Li Q et al (2014) Combined fenobam and amantadine treatment promotes robust antidyskinetic effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of Parkinson’s disease. Mov Disord 29:772–779. doi: 10.1002/mds.25859 PubMedCrossRefGoogle Scholar
  85. Kobylecki C, Hill MP, Crossman AR, Ravenscroft P (2011) Synergistic antidyskinetic effects of topiramate and amantadine in animal models of Parkinson’s disease. Mov Disord 26:2354–2363. doi: 10.1002/mds.23867 PubMedCrossRefGoogle Scholar
  86. Koprich JB, Fox SH, Johnston TH et al (2011) The selective mu-opioid receptor antagonist ADL5510 reduces levodopa-induced dyskinesia without affecting antiparkinsonian action in MPTP-lesioned macaque model of Parkinson’s disease. Mov Disord 26:1225–1233. doi: 10.1002/mds.23631 PubMedCrossRefGoogle Scholar
  87. Koprich JB, Johnston TH, Reyes G et al (2016) Towards a non-human primate model of alpha-synucleinopathy for development of therapeutics for Parkinson’s disease: optimization of AAV1/2 delivery parameters to drive sustained expression of alpha synuclein and dopaminergic degeneration in macaque. PLoS One 11:e0167235. doi: 10.1371/journal.pone.0167235 PubMedPubMedCentralCrossRefGoogle Scholar
  88. Kordower JH, Palfi S, Chen EY et al (1999) Clinicopathological findings following intraventricular glial-derived neurotrophic factor treatment in a patient with Parkinson’s disease. Ann Neurol 46:419–424PubMedCrossRefGoogle Scholar
  89. Kordower JH, Emborg ME, Bloch J et al (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease. Science 290:767–773PubMedCrossRefGoogle Scholar
  90. Kordower JH, Herzog CD, Dass B et al (2006) Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys. Ann Neurol 60:706–715. doi: 10.1002/ana.21032 PubMedCrossRefGoogle Scholar
  91. Krack P, Martinez-Fernandez R, del Alamo M, Obeso JA (2017) Current applications and limitations of surgical treatments for movement disorders. Mov Disord 32:36–52. doi: 10.1002/mds.26890 PubMedCrossRefGoogle Scholar
  92. Kupsch A, Sautter J, Götz ME et al (2001) Monoamine oxidase-inhibition and MPTP-induced neurotoxicity in the non-human primate: comparison of rasagiline (TVP 1012) with selegiline. J Neural Transm 108:985–1009. doi: 10.1007/s007020170018 PubMedCrossRefGoogle Scholar
  93. Laitinen LV, Bergenheim AT, Hariz MI (1992) Ventroposterolateral pallidotomy can abolish all parkinsonian symptoms. Stereotact Funct Neurosurg 58:14–21PubMedCrossRefGoogle Scholar
  94. Langston JW, Forno LS, Rebert CS, Irwin I (1984) Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey. Brain Res 292:390–394PubMedCrossRefGoogle Scholar
  95. Lee JM, Derkinderen P, Kordower JH et al (2017) The search for a peripheral biopsy indicator of α-synuclein pathology for Parkinson disease. J Neuropathol Exp Neurol nlw103. doi: 10.1093/jnen/nlw103
  96. Lees AJ, Hardy J, Revesz T (2009) Parkinson’s disease. Lancet 373:2055–2066. doi: 10.1016/S0140-6736(09)60492-X PubMedCrossRefGoogle Scholar
  97. Leinenga G, Gotz J (2015) Scanning ultrasound removes amyloid- and restores memory in an Alzheimer’s disease mouse model. Sci Transl Med 7:278ra33–278ra33. doi: 10.1126/scitranslmed.aaa2512
  98. Leinenga G, Langton C, Nisbet R, Götz J (2016) Ultrasound treatment of neurological diseases—current and emerging applications. Nat Rev Neurol 12:161–174. doi: 10.1038/nrneurol.2016.13 PubMedCrossRefGoogle Scholar
  99. Lenka A, Hegde S, Arumugham SS, Pal PK (2016a) Pattern of cognitive impairment in patients with Parkinson’s disease and psychosis: a critical review. Parkinsonism Relat Disord. doi: 10.1016/j.parkreldis.2016.12.025 Google Scholar
  100. Lenka A, Hegde S, Jhunjhunwala KR, Pal PK (2016b) Interactions of visual hallucinations, rapid eye movement sleep behavior disorder and cognitive impairment in Parkinson’s disease: a review. Parkinsonism Relat Disord 22:1–8. doi: 10.1016/j.parkreldis.2015.11.018 PubMedCrossRefGoogle Scholar
  101. LeWitt PA, Fahn S (2016) Levodopa therapy for Parkinson disease: table. Neurology 86:S3–S12. doi: 10.1212/WNL.0000000000002509 PubMedCrossRefGoogle Scholar
  102. LeWitt PA, Rezai AR, Leehey MA et al (2011) AAV2-GAD gene therapy for advanced Parkinson’s disease: a double-blind, sham-surgery controlled, randomised trial. Lancet Neurol 10:309–319. doi: 10.1016/S1474-4422(11)70039-4 PubMedCrossRefGoogle Scholar
  103. Limousin P, Pollak P, Benazzouz A et al (1995) Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet (London, England) 345:91–95Google Scholar
  104. Limousin P, Pollak P, Benazzouz A et al (1995b) Bilateral subthalamic nucleus stimulation for severe Parkinson’s disease. Mov Disord 10:672–674. doi: 10.1002/mds.870100523 PubMedCrossRefGoogle Scholar
  105. Ma Y, Peng S, Spetsieris PG et al (2012) Abnormal metabolic brain networks in a nonhuman primate model of parkinsonism. J Cereb Blood Flow Metab 32:633–642. doi: 10.1038/jcbfm.2011.166 PubMedCrossRefGoogle Scholar
  106. Marks WJ Jr, Ostrem JL, Verhagen L et al (2008) Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson’s disease: an open-label, phase I trial. Lancet Neurol 7:400–408PubMedCrossRefGoogle Scholar
  107. Marks WJ, Bartus RT, Siffert J et al (2010) Gene delivery of AAV2-neurturin for Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol 9:1164–1172. doi: 10.1016/S1474-4422(10)70254-4 PubMedCrossRefGoogle Scholar
  108. Martin JP (1927) Hemichorea resulting from a local lesion of the brain (the syndrome of the body of luys). Brain 50:637–649. doi: 10.1093/brain/50.3-4.637 CrossRefGoogle Scholar
  109. Martínez-Fernández R, Schmitt E, Martinez-Martin P, Krack P (2016) The hidden sister of motor fluctuations in Parkinson’s disease: a review on nonmotor fluctuations. Mov Disord 31:1080–1094. doi: 10.1002/mds.26731 PubMedCrossRefGoogle Scholar
  110. McDannold N, Arvanitis CD, Vykhodtseva N, Livingstone MS (2012) Temporary disruption of the blood-brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques. Cancer Res 72:3652–3663. doi: 10.1158/0008-5472.CAN-12-0128 PubMedPubMedCentralCrossRefGoogle Scholar
  111. Miller WC, De Long MR (1987) Altered tonic activity of neurons in the globus pallidus and subthalamic nucleus in the primate MPTP model of parkinsonism. In: Carpenter MB, Jayaraman A (eds) The basal ganglia II. Plenum Press, New York, pp 415–427CrossRefGoogle Scholar
  112. Miller GM, Yatin SM, De La Garza R et al (2001) Cloning of dopamine, norepinephrine and serotonin transporters from monkey brain: relevance to cocaine sensitivity. Brain Res Mol Brain Res 87:124–143PubMedCrossRefGoogle Scholar
  113. Mitchell IJ, Clarke CE, Boyce S et al (1989) Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroscience 32:213–226PubMedCrossRefGoogle Scholar
  114. Moehle MS, Webber PJ, Tse T et al (2012) LRRK2 inhibition attenuates microglial inflammatory responses. J Neurosci 32:1602–1611. doi: 10.1523/JNEUROSCI.5601-11.2012 PubMedPubMedCentralCrossRefGoogle Scholar
  115. Morin N, Morissette M, Grégoire L et al (2015a) Contribution of brain serotonin subtype 1B receptors in levodopa-induced motor complications. Neuropharmacology 99:356–368. doi: 10.1016/j.neuropharm.2015.08.002 PubMedCrossRefGoogle Scholar
  116. Morin N, Morissette M, Grégoire L, Di Paolo T (2015b) Effect of a chronic treatment with an mGlu5 receptor antagonist on brain serotonin markers in parkinsonian monkeys. Prog Neuro-Psychopharmacol Biol Psychiatry 56:27–38. doi: 10.1016/j.pnpbp.2014.07.006 CrossRefGoogle Scholar
  117. Morin N, Morissette M, Grégoire L, Di Paolo T (2016) mGlu5, dopamine D2 and adenosine A2A receptors in l-DOPA-induced dyskinesias. Curr Neuropharmacol 14:481–493PubMedPubMedCentralCrossRefGoogle Scholar
  118. Morissette M, Morin N, Grégoire L et al (2016) Brain α7 nicotinic acetylcholine receptors in MPTP-lesioned monkeys and parkinsonian patients. Biochem Pharmacol 109:62–69. doi: 10.1016/j.bcp.2016.03.023 PubMedCrossRefGoogle Scholar
  119. Muramatsu S-I, Fujimoto K-I, Ikeguchi K et al (2002) Behavioral recovery in a primate model of Parkinson’s disease by triple transduction of striatal cells with adeno-associated viral vectors expressing dopamine-synthesizing enzymes. Hum Gene Ther 13:345–354. doi: 10.1089/10430340252792486 PubMedCrossRefGoogle Scholar
  120. Nader MA, Czoty PW (2008) Brain imaging in nonhuman primates: insights into drug addiction. ILAR J 49:89–102PubMedCrossRefGoogle Scholar
  121. Nutt JG, Burchiel KJ, Comella CL et al (2003) Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology 60:69–73PubMedCrossRefGoogle Scholar
  122. Obeso JA, Rodriguez MC, Guridi J et al (2001) Lesion of the basal ganglia and surgery for Parkinson disease. Arch Neurol 58:1165–1166PubMedCrossRefGoogle Scholar
  123. Obeso JA, Rodriguez-Oroz MC, Stamelou M et al (2014) The expanding universe of disorders of the basal ganglia. Lancet 384:523–531. doi: 10.1016/S0140-6736(13)62418-6 PubMedCrossRefGoogle Scholar
  124. Oertel W, Schulz JB (2016) Current and experimental treatments of Parkinson disease: a guide for neuroscientists. J Neurochem. doi: 10.1111/jnc.13750 Google Scholar
  125. Olanow CW (2009) Can we achieve neuroprotection with currently available anti-parkinsonian interventions? Neurology 72:S59–S64. doi: 10.1212/WNL.0b013e318199068b PubMedCrossRefGoogle Scholar
  126. Palfi S, Leventhal L, Chu Y et al (2002) Lentivirally delivered glial cell line-derived neurotrophic factor increases the number of striatal dopaminergic neurons in primate models of nigrostriatal degeneration. J Neurosci 22:4942–4954PubMedGoogle Scholar
  127. Pan J, Cai H (2017) Opioid system in l-DOPA-induced dyskinesia. Transl Neurodegener 6:1. doi: 10.1186/s40035-017-0071-y PubMedPubMedCentralCrossRefGoogle Scholar
  128. Parkinson J (1817) An essay on the shaking palsy. J Neuropsychiatry Clin Neurosci 14:223–236CrossRefGoogle Scholar
  129. Pearce RK, Jackson M, Smith L et al (1995) Chronic l-DOPA administration induces dyskinesias in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmoset (Callithrix jacchus). Mov Disord 10:731–740. doi: 10.1002/mds.870100606 PubMedCrossRefGoogle Scholar
  130. Péchadre JC, Larochelle L, Poirier LJ (1976) Parkinsonian akinesia, rigidity and tremor in the monkey. Histopathological and neuropharmacological study. J Neurol Sci 28:147–157PubMedCrossRefGoogle Scholar
  131. Pessiglione M, Guehl D, Hirsch EC et al (2004) Disruption of self-organized actions in monkeys with progressive MPTP-induced parkinsonism. I. Effects of task complexity. Eur J Neurosci 19:426–436PubMedCrossRefGoogle Scholar
  132. Phillips KA, Ross CN, Spross J et al (2017) Behavioral phenotypes associated with MPTP induction of partial lesions in common marmosets (Callithrix jacchus). Behav Brain Res. doi: 10.1016/j.bbr.2017.02.010 Google Scholar
  133. Pignataro D, Sucunza D, Rico AJ et al (2017) Gene therapy approaches in the non-human primate model of Parkinson’s disease. J Neural Transm. doi: 10.1007/s00702-017-1681-3 PubMedGoogle Scholar
  134. Pinna A, Ko WKD, Costa G et al (2016) Antidyskinetic effect of A2A and 5HT1A/1B receptor ligands in two animal models of Parkinson’s disease. Mov Disord 31:501–511. doi: 10.1002/mds.26475 PubMedCrossRefGoogle Scholar
  135. Poirier LJ (1960) Experimental and histological study of midbrain dyskinesias. J Neurophysiol 23:534–551PubMedCrossRefGoogle Scholar
  136. Poirier LJ, Lafleur J, de Lean J et al (1974) Physiopathology of the cerebellum in the monkey. 2. Motor disturbances associated with partial and complete destruction of cerebellar structures. J Neurol Sci 22:491–509PubMedCrossRefGoogle Scholar
  137. Pollak P, Benabid AL, Gross C et al (1993) Effects of the stimulation of the subthalamic nucleus in Parkinson disease. Rev Neurol (Paris) 149:175–176Google Scholar
  138. Pont-Sunyer C, Iranzo A, Gaig C et al (2015) Sleep disorders in parkinsonian and nonparkinsonian LRRK2 mutation carriers. PLoS One 10:e0132368. doi: 10.1371/journal.pone.0132368 PubMedPubMedCentralCrossRefGoogle Scholar
  139. Postuma RB, Gagnon J-F, Vendette M, Montplaisir JY (2009) Idiopathic REM sleep behavior disorder in the transition to degenerative disease. Mov Disord 24:2225–2232. doi: 10.1002/mds.22757 PubMedCrossRefGoogle Scholar
  140. Potts LF, Park ES, Woo J-M et al (2015) Dual κ-agonist/μ-antagonist opioid receptor modulation reduces levodopa-induced dyskinesia and corrects dysregulated striatal changes in the nonhuman primate model of Parkinson disease. Ann Neurol 77:930–941. doi: 10.1002/ana.24375 PubMedCrossRefGoogle Scholar
  141. Prescott MJ (2010) Ethics of primate use. Adv Sci Res 5:11–22. doi: 10.5194/asr-5-11-2010 CrossRefGoogle Scholar
  142. Quik M, Perez XA, Bordia T (2012) Nicotine as a potential neuroprotective agent for Parkinson’s disease. Mov Disord 27:947–957. doi: 10.1002/mds.25028 PubMedPubMedCentralCrossRefGoogle Scholar
  143. Recasens A, Dehay B, Bové J et al (2014a) Lewy body extracts from Parkinson disease brains trigger α-synuclein pathology and neurodegeneration in mice and monkeys. Ann Neurol 75:351–362. doi: 10.1002/ana.24066 PubMedCrossRefGoogle Scholar
  144. Recasens A, Dehay B, Carballo-Carbajal I et al (2014) Lewy body extracts from Parkinson’s disease brain trigger alfa-synuclein pathology and neurodegeneration in mice and monkeys. Ann Neurol 351–362Google Scholar
  145. Riahi G, Morissette M, Parent M, Di Paolo T (2011) Brain 5-HT2A receptors in MPTP monkeys and levodopa-induced dyskinesias. Eur J Neurosci 33:1823–1831. doi: 10.1111/j.1460-9568.2011.07675.x PubMedCrossRefGoogle Scholar
  146. Rodríguez-Nogales C, Garbayo E, Carmona-Abellán MM et al (2016) Brain aging and Parkinson’s disease: new therapeutic approaches using drug delivery systems. Maturitas 84:25–31. doi: 10.1016/j.maturitas.2015.11.009 PubMedCrossRefGoogle Scholar
  147. Rodriguez-Oroz MC, Jahanshahi M, Krack P et al (2009) Initial clinical manifestations of Parkinson’s disease: features and pathophysiological mechanisms. Lancet Neurol 8:1128–1139. doi: 10.1016/S1474-4422(09)70293-5 PubMedCrossRefGoogle Scholar
  148. Roy M, Cardoso C, Dorieux O et al (2015) Age-associated evolution of plasmatic amyloid in mouse lemur primates: relationship with intracellular amyloid deposition. Neurobiol Aging 36:149–156. doi: 10.1016/j.neurobiolaging.2014.07.017 PubMedCrossRefGoogle Scholar
  149. Rylander D, Iderberg H, Li Q et al (2010) A mGluR5 antagonist under clinical development improves l-DOPA-induced dyskinesia in parkinsonian rats and monkeys. Neurobiol Dis 39:352–361. doi: 10.1016/j.nbd.2010.05.001 PubMedCrossRefGoogle Scholar
  150. Schneider JS (1990) Chronic exposure to low doses of MPTP. II. Neurochemical and pathological consequences in cognitively-impaired, motor asymptomatic monkeys. Brain Res 534:25–36PubMedCrossRefGoogle Scholar
  151. Schneider JS, Kovelowski CJ 2nd (1990) Chronic exposure to low doses of MPTP. I. Cognitive deficits in motor asymptomatic monkeys. Brain Res 519:122–128PubMedCrossRefGoogle Scholar
  152. Shimozawa A, Ono M, Takahara D et al (2017) Propagation of pathological α-synuclein in marmoset brain. Acta Neuropathol Commun 5:12. doi: 10.1186/s40478-017-0413-0 PubMedPubMedCentralCrossRefGoogle Scholar
  153. Spillantini MG, Schmidt ML, Lee VM et al (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840PubMedCrossRefGoogle Scholar
  154. Stoessl AJ, Lehericy S, Strafella AP (2014) Imaging insights into basal ganglia function, Parkinson’s disease, and dystonia. Lancet 384:532–544. doi: 10.1016/S0140-6736(14)60041-6 PubMedPubMedCentralCrossRefGoogle Scholar
  155. Strafella AP, Bohnen NI, Perlmutter JS et al (2017) Molecular imaging to track Parkinson’s disease and atypical parkinsonisms: new imaging frontiers. Mov Disord 32:181–192. doi: 10.1002/mds.26907 PubMedCrossRefGoogle Scholar
  156. Surmeier DJ, Obeso JA, Halliday GM (2017) Selective neuronal vulnerability in Parkinson disease. Nat Rev Neurosci 18:101–113. doi: 10.1038/nrn.2016.178
  157. Tabbal SD, Mink JW, Antenor JAV et al (2006) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced acute transient dystonia in monkeys associated with low striatal dopamine. Neuroscience 141:1281–1287. doi: 10.1016/j.neuroscience.2006.04.072 PubMedCrossRefGoogle Scholar
  158. Taylor JR, Elsworth JD, Roth RH et al (1990) Cognitive and motor deficits in the acquisition of an object retrieval/detour task in MPTP-treated monkeys. Brain 617–37Google Scholar
  159. Taylor JR, Roth RH, Sladek JR, Redmond DE (1990b) Cognitive and motor deficits in the performance of an object retrieval task with a barrier-detour in monkeys (Cercopithecus aethiops sabaeus) treated with MPTP: long-term performance and effect of transparency of the barrier. Behav Neurosci 104:564–576PubMedCrossRefGoogle Scholar
  160. Tian L, Xia Y, Flores HP et al (2015) Neuroimaging analysis of the dopamine basis for apathetic behaviors in an MPTP-lesioned primate model. PLoS One 10:e0132064. doi: 10.1371/journal.pone.0132064 PubMedPubMedCentralCrossRefGoogle Scholar
  161. Tysnes O-B, Storstein A (2017) Epidemiology of Parkinson’s disease. J Neural Transm. doi: 10.1007/s00702-017-1686-y PubMedGoogle Scholar
  162. Uchida S, Soshiroda K, Okita E et al (2015) The adenosine A2A receptor antagonist, istradefylline enhances anti-parkinsonian activity induced by combined treatment with low doses of l-DOPA and dopamine agonists in MPTP-treated common marmosets. Eur J Pharmacol 766:25–30. doi: 10.1016/j.ejphar.2015.09.028 PubMedCrossRefGoogle Scholar
  163. Valdés P, Schneider BL (2016) Gene therapy: a promising approach for neuroprotection in Parkinson’s disease? Front Neuroanat 10:123. doi: 10.3389/fnana.2016.00123 PubMedPubMedCentralCrossRefGoogle Scholar
  164. Vanhauwaert R, Verstreken P (2015) Flies with Parkinson’s disease. Exp Neurol 274:42–51. doi: 10.1016/j.expneurol.2015.02.020 PubMedCrossRefGoogle Scholar
  165. Verdier J-M, Acquatella I, Lautier C et al (2015) Lessons from the analysis of nonhuman primates for understanding human aging and neurodegenerative diseases. Front Neurosci 9:64. doi: 10.3389/fnins.2015.00064 PubMedPubMedCentralCrossRefGoogle Scholar
  166. Verhave PS, Jongsma MJ, Van den Berg RM et al (2011) REM sleep behavior disorder in the marmoset MPTP model of early Parkinson disease. Sleep 34:1119–1125. doi: 10.5665/SLEEP.1174 PubMedPubMedCentralCrossRefGoogle Scholar
  167. Vezoli J, Fifel K, Leviel V et al (2011) Early presymptomatic and long-term changes of rest activity cycles and cognitive behavior in a MPTP-monkey model of Parkinson’s disease. PLoS One 6:e23952. doi: 10.1371/journal.pone.0023952 PubMedPubMedCentralCrossRefGoogle Scholar
  168. Visanji NP, Gomez-Ramirez J, Johnston TH et al (2006) Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson’s disease. Mov Disord 21:1879–1891. doi: 10.1002/mds.21073 PubMedCrossRefGoogle Scholar
  169. Visanji NP, Brotchie JM, Kalia LV et al (2016) α-Synuclein-based animal models of Parkinson’s disease: challenges and opportunities in a new era. Trends Neurosci 39:750–762. doi: 10.1016/j.tins.2016.09.003 PubMedCrossRefGoogle Scholar
  170. Vitale A, Manciocco A, Alleva E (2009) The 3R principle and the use of non-human primates in the study of neurodegenerative diseases: the case of Parkinson’s disease. Neurosci Biobehav Rev 33:33–47. doi: 10.1016/j.neubiorev.2008.08.006 PubMedCrossRefGoogle Scholar
  171. Weaver FM, Follett K, Stern M et al (2009) Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA 301:63–73. doi: 10.1001/jama.2008.929 PubMedPubMedCentralCrossRefGoogle Scholar
  172. Weed MR, Woolverton WL, Paul IA (1998) Dopamine D1 and D2 receptor selectivities of phenyl-benzazepines in rhesus monkey striata. Eur J Pharmacol 361:129–142PubMedCrossRefGoogle Scholar
  173. Weerts EM, Fantegrossi WE, Goodwin AK (2007) The value of nonhuman primates in drug abuse research. Exp Clin Psychopharmacol 15:309–327. doi: 10.1037/1064-1297.15.4.309 PubMedCrossRefGoogle Scholar
  174. Weintraub D, Simuni T, Caspell-Garcia C et al (2015) Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson’s disease. Mov Disord 30:919–927. doi: 10.1002/mds.26170 PubMedPubMedCentralCrossRefGoogle Scholar
  175. Whittier JR (1948) Rhesus hyperkinesia by subthalamic lesion. Fed Proc 7:133PubMedGoogle Scholar
  176. Whittier JR, Mettler FA (1947) Subthalamic lesion in the primate. Fed Proc 6:226PubMedGoogle Scholar
  177. Wichmann T, Bergman H, DeLong MR (1994) The primate subthalamic nucleus. III. Changes in motor behavior and neuronal activity in the internal pallidum induced by subthalamic inactivation in the MPTP model of parkinsonism. J Neurophysiol 72(2):521–530Google Scholar
  178. Yang W, Wang G, Wang C-E et al (2015) Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain. J Neurosci 35:8345–8358. doi: 10.1523/JNEUROSCI.0772-15.2015 PubMedPubMedCentralCrossRefGoogle Scholar
  179. Zhan W, Kang GA, Glass GA et al (2012) Regional alterations of brain microstructure in Parkinson’s disease using diffusion tensor imaging. Mov Disord 27:90–97. doi: 10.1002/mds.23917 PubMedCrossRefGoogle Scholar
  180. Zhang D, Bordia T, McGregor M et al (2014a) ABT-089 and ABT-894 reduce levodopa-induced dyskinesias in a monkey model of Parkinson’s disease. Mov Disord 29:508–517. doi: 10.1002/mds.25817 PubMedPubMedCentralCrossRefGoogle Scholar
  181. Zhang D, McGregor M, Decker MW, Quik M (2014b) The 7 nicotinic receptor agonist ABT-107 decreases l-Dopa-induced dyskinesias in parkinsonian monkeys. J Pharmacol Exp Ther 351:25–32. doi: 10.1124/jpet.114.216283 PubMedPubMedCentralCrossRefGoogle Scholar
  182. Zhang D, McGregor M, Bordia T et al (2015) α7 nicotinic receptor agonists reduce levodopa-induced dyskinesias with severe nigrostriatal damage. Mov Disord 30:1901–1911. doi: 10.1002/mds.26453 PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2017

Authors and Affiliations

  • Javier Blesa
    • 1
    • 2
  • Inés Trigo-Damas
    • 1
    • 2
  • Natalia López-González del Rey
    • 1
    • 2
  • José A. Obeso
    • 1
    • 2
  1. 1.HM CINACHospital Universitario HM Puerta del SurMadridSpain
  2. 2.Biomedical Research Center of Neurodegenerative Diseases (CIBERNED)MadridSpain

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