Do alpha-synuclein vector injections provide a better model of Parkinson's disease than the classic 6-hydroxydopamine model?

Experimental Neurology

Volumn 237, Issue 1, 2012, Pages 36-42

  Lindgren, Hanna S ^a,b   Lelos, Mariah J ^a,b   Dunnett, Stephen B ^a,b  

^a CARDIFF UNIVERSITY   (United Kingdom)

^b Life Sciences Building ^*  (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN; DOPAMINE; NORADRENALIN; OXIDOPAMINE; PARVOVIRUS VECTOR; SEROTONIN;

ANIMAL MODEL; BEHAVIOR DISORDER; DISEASE MODEL; DOPAMINERGIC NERVE CELL; GENE FUNCTION; GENE OVEREXPRESSION; IMMUNOREACTIVITY; MOTOR DEVELOPMENT; MOTOR DYSFUNCTION; NEUROPATHOLOGY; NONHUMAN; NOTE; PARKINSON DISEASE; PHENOTYPE; PREDICTIVE VALUE; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN EXPRESSION; RAT; SEROTONINERGIC SYSTEM; SUBSTANTIA NIGRA PARS COMPACTA;

ALPHA-SYNUCLEIN; ANIMALS; DISEASE MODELS, ANIMAL; GENETIC VECTORS; HUMANS; OXIDOPAMINE; PARKINSON DISEASE; PARKINSON DISEASE, SECONDARY; RATS;

EID: 84863701701     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2012.05.022     Document Type: Note

References (95)

1. Barkholt P., Sanchez-Guajardo V., Kirik D., Romero-Ramos M. Long-term polarization of microglia upon alpha-synuclein overexpression in nonhuman primates. Neuroscience 2012, 208:85-96.
2. Beal M.F. Mitochondria take center stage in aging and neurodegeneration. Ann. Neurol. 2005, 58:495-505.
3. Betarbet R., Sherer T.B., MacKenzie G., Garcia-Osuna M., Panov A.V., Greenamyre J.T. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat. Neurosci. 2000, 3:1301-1306.
4. Bjorklund A., Rosenblad C., Winkler C., Kirik D. Studies on neuroprotective and regenerative effects of GDNF in a partial lesion model of Parkinson's disease. Neurobiol. Dis. 1997, 4:186-200.
5. Cao S., Theodore S., Standaert D.G. Fcgamma receptors are required for NF-kappaB signaling, microglial activation and dopaminergic neurodegeneration in an AAV-synuclein mouse model of Parkinson's disease. Mol. Neurodegener. 2010, 5:42.
6. Cenci M.A., Whishaw I.Q., Schallert T. Animal models of neurological deficits: how relevant is the rat?. Nat. Rev. Neurosci. 2002, 3:574-579.
7. Chung C.Y., Koprich J.B., Siddiqi H., Isacson O. Dynamic changes in presynaptic and axonal transport proteins combined with striatal neuroinflammation precede dopaminergic neuronal loss in a rat model of AAV alpha-synucleinopathy. J. Neurosci. 2009, 29:3365-3373.
8. Colla E., Jensen P.H., Pletnikova O., Troncoso J.C., Glabe C., Lee M.K. Accumulation of toxic alpha-synuclein oligomer within endoplasmic reticulum occurs in alpha-synucleinopathy in vivo. J. Neurosci. 2012, 32:3301-3305.
9. Cordeiro K.K., Jiang W., Papazoglou A., Tenorio S.B., Dobrossy M., Nikkhah G. Graft-mediated functional recovery on a skilled forelimb use paradigm in a rodent model of Parkinson's disease is dependent on reward contingency. Behav. Brain Res. 2010, 212:187-195.
10. Dauer W., Przedborski S. Parkinson's disease: mechanisms and models. Neuron 2003, 39:889-909.
11. Decressac M., Ulusoy A., Mattsson B., Georgievska B., Romero-Ramos M., Kirik D., Bjorklund A. GDNF fails to exert neuroprotection in a rat alpha-synuclein model of Parkinson's disease. Brain 2011, 134:2302-2311.
12. Decressac M., Mattsson B., Bjorklund A. Comparison of the behavioural and histological characteristics of the 6-OHDA and alpha-synuclein rat models of Parkinson's disease. Exp. Neurol. 2012, 235(1):306-315.
13. Decressac M., Mattsson B., Lundblad M., Weikop P., Bjorklund A. Progressive neurodegenerative and behavioural changes induced by AAV-mediated overexpression of alpha-synuclein in midbrain dopamine neurons. Neurobiol. Dis. 2012, 45:939-953.
14. Dong Z., Ferger B., Feldon J., Bueler H. Overexpression of Parkinson's disease-associated alpha-synucleinA53T by recombinant adeno-associated virus in mice does not increase the vulnerability of dopaminergic neurons to MPTP. J. Neurobiol. 2002, 53:1-10.
15. Dowd E., Monville C., Torres E.M., Dunnett S.B. The Corridor Task: a simple test of lateralised response selection sensitive to unilateral dopamine deafferentation and graft-derived dopamine replacement in the striatum. Brain Res. Bull. 2005, 68:24-30.
16. Eslamboli A., Baker H.F., Ridley R.M., Annett L.E. Sensorimotor deficits in a unilateral intrastriatal 6-OHDA partial lesion model of Parkinson's disease in marmoset monkeys. Exp. Neurol. 2003, 183:418-429.
17. Eslamboli A., Romero-Ramos M., Burger C., Bjorklund T., Muzyczka N., Mandel R.J., Baker H., Ridley R.M., Kirik D. Long-term consequences of human alpha-synuclein overexpression in the primate ventral midbrain. Brain 2007, 130:799-815.
18. Esteves A.R., Arduino D.M., Silva D.F., Oliveira C.R., Cardoso S.M. Mitochondrial dysfunction: the road to alpha-synuclein oligomerization in PD. Parkinsons Dis. 2011, 2011:693761.
19. Fulceri F., Biagioni F., Lenzi P., Falleni A., Gesi M., Ruggieri S., Fornai F. Nigrostriatal damage with 6-OHDA: validation of routinely applied procedures. Ann. N. Y. Acad. Sci. 2006, 1074:344-348.
20. Gash D.M., Zhang Z., Ovadia A., Cass W.A., Yi A., Simmerman L., Russell D., Martin D., Lapchak P.A., Collins F., Hoffer B.J., Gerhardt G.A. Functional recovery in Parkinsonian monkeys treated with GDNF. Nature 1996, 380:252-255.
21. Georgievska B., Kirik D., Rosenblad C., Lundberg C., Bjorklund A. Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector. Neuroreport 2002, 13:75-82.
22. Gill S.S., Patel N.K., Hotton G.R., O'Sullivan K., McCarter R., Bunnage M., Brooks D.J., Svendsen C.N., Heywood P. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat. Med. 2003, 9:589-595.
23. Gomez-Isla T., Irizarry M.C., Mariash A., Cheung B., Soto O., Schrump S., Sondel J., Kotilinek L., Day J., Schwarzschild M.A., Cha J.H., Newell K., Miller D.W., Ueda K., Young A.B., Hyman B.T., Ashe K.H. Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha-synuclein A30P transgenic mice. Neurobiol. Aging 2003, 24:245-258.
24. Graham D.R., Sidhu A. Mice expressing the A53T mutant form of human alpha-synuclein exhibit hyperactivity and reduced anxiety-like behavior. J. Neurosci. Res. 2010, 88:1777-1783.
25. Graybiel A.M., Aosaki T., Flaherty A.W., Kimura M. The basal ganglia and adaptive motor control. Science 1994, 265:1826-1831.
26. Hald A., Lotharius J. Oxidative stress and inflammation in Parkinson's disease: is there a causal link?. Exp. Neurol. 2005, 193:279-290.
27. Halliday G.M., Li Y.W., Blumbergs P.C., Joh T.H., Cotton R.G., Howe P.R., Blessing W.W., Geffen L.B. Neuropathology of immunohistochemically identified brainstem neurons in Parkinson's disease. Ann. Neurol. 1990, 27:373-385.
28. Hefti F., Melamed E., Sahakian B.J., Wurtman R.J. Circling behavior in rats with partial, unilateral nigro-striatal lesions: effect of amphetamine, apomorphine, and DOPA. Pharmacol. Biochem. Behav. 1980, 12:185-188.
29. Hudson J.L., van Horne C.G., Stromberg I., Brock S., Clayton J., Masserano J., Hoffer B.J., Gerhardt G.A. Correlation of apomorphine- and amphetamine-induced turning with nigrostriatal dopamine content in unilateral 6-hydroxydopamine lesioned rats. Brain Res. 1993, 626:167-174.
30. Imai Y., Lu B. Mitochondrial dynamics and mitophagy in Parkinson's disease: disordered cellular power plant becomes a big deal in a major movement disorder. Curr. Opin. Neurobiol. 2011, 21:935-941.
31. Iwamoto E.T., Loh H.H., Way E.L. Circling behavior in rats with 6-hydroxydopamine or electrolytic nigral lesions. Eur. J. Pharmacol. 1976, 37:339-356.
32. Kirik D., Rosenblad C., Bjorklund A. Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat. Exp. Neurol. 1998, 152:259-277.
33. Kirik D., Georgievska B., Rosenblad C., Bjorklund A. Delayed infusion of GDNF promotes recovery of motor function in the partial lesion model of Parkinson's disease. Eur. J. Neurosci. 2001, 13:1589-1599.
34. Kirik D., Rosenblad C., Burger C., Lundberg C., Johansen T.E., Muzyczka N., Mandel R.J., Bjorklund A. Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. J. Neurosci. 2002, 22:2780-2791.
35. Kirik D., Annett L.E., Burger C., Muzyczka N., Mandel R.J., Bjorklund A. 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. U. S. A. 2003, 100:2884-2889.
36. Kirik D., Georgievska B., Bjorklund A. Localized striatal delivery of GDNF as a treatment for Parkinson disease. Nat. Neurosci. 2004, 7:105-110.
37. Klein R.L., King M.A., Hamby M.E., Meyer E.M. Dopaminergic cell loss induced by human A30P alpha-synuclein gene transfer to the rat substantia nigra. Hum. Gene Ther. 2002, 13:605-612.
38. Klein R.L., Dayton R.D., Leidenheimer N.J., Jansen K., Golde T.E., Zweig R.M. Efficient neuronal gene transfer with AAV8 leads to neurotoxic levels of tau or green fluorescent proteins. Mol. Ther. 2006, 13:517-527.
39. Koprich J.B., Johnston T.H., Reyes M.G., Sun X., Brotchie J.M. Expression of human A53T alpha-synuclein in the rat substantia nigra using a novel AAV1/2 vector produces a rapidly evolving pathology with protein aggregation, dystrophic neurite architecture and nigrostriatal degeneration with potential to model the pathology of Parkinson's disease. Mol. Neurodegener. 2010, 5:43.
40. Koprich J.B., Johnston T.H., Huot P., Reyes M.G., Espinosa M., Brotchie J.M. Progressive neurodegeneration or endogenous compensation in an animal model of Parkinson's disease produced by decreasing doses of alpha-synuclein. PLoS One 2011, 6:e17698.
41. Kordower J.H., Chu Y., Hauser R.A., Freeman T.B., Olanow C.W. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat. Med. 2008, 14:504-506.
42. Kornum B.R., Stott S.R., Mattsson B., Wisman L., Ettrup A., Hermening S., Knudsen G.M., Kirik D. Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain. Exp. Neurol. 2010, 222:70-85.
43. Lang A.E., Gill S., Patel N.K., Lozano A., Nutt J.G., Penn R., Brooks D.J., Hotton G., Moro E., Heywood P., Brodsky M.A., Burchiel K., Kelly P., Dalvi A., Scott B., Stacy M., Turner D., Wooten V.G., Elias W.J., Laws E.R., Dhawan V., Stoessl A.J., Matcham J., Coffey R.J., Traub M. Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann. Neurol. 2006, 59:459-466.
44. Langston J.W., Ballard P., Tetrud J.W., Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983, 219:979-980.
45. Lauwers E., Debyser Z., Van Dorpe J., De Strooper B., Nuttin B., Baekelandt V. Neuropathology and neurodegeneration in rodent brain induced by lentiviral vector-mediated overexpression of alpha-synuclein. Brain Pathol. 2003, 13:364-372.
46. Li J.Y., Englund E., Holton J.L., Soulet D., Hagell P., Lees A.J., Lashley T., Quinn N.P., Rehncrona S., Bjorklund A., Widner H., Revesz T., Lindvall O., Brundin P. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat. Med. 2008, 14:501-503.
47. Li J.Y., Englund E., Widner H., Rehncrona S., Bjorklund A., Lindvall O., Brundin P. Characterization of Lewy body pathology in 12- and 16-year-old intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease. Mov. Disord. 2010, 25:1091-1096.
48. Lindgren, H.S., Dunnett, S.B., accepted for publication. Cognitive dysfunction and depression in Parkinson's disease - What can be learned from rodent models? Eur. J. Neurosci. 35(12), 1894-907.
49. Lindgren H.S., Andersson D.R., Lagerkvist S., Nissbrandt H., Cenci M.A. l-DOPA-induced dopamine efflux in the striatum and the substantia nigra in a rat model of Parkinson's disease: temporal and quantitative relationship to the expression of dyskinesia. J. Neurochem. 2010, 112:1465-1476.
50. Liu H.S., Jan M.S., Chou C.K., Chen P.H., Ke N.J. Is green fluorescent protein toxic to the living cells?. Biochem. Biophys. Res. Commun. 1999, 260:712-717.
51. Lo Bianco C., Ridet J.L., Schneider B.L., Deglon N., Aebischer P. alpha-Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson's disease. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:10813-10818.
52. Lo Bianco C., Deglon N., Pralong W., Aebischer P. Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a genetic rat model of Parkinson's disease. Neurobiol. Dis. 2004, 17:283-289.
53. Lo Bianco C., Schneider B.L., Bauer M., Sajadi A., Brice A., Iwatsubo T., Aebischer P. Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an alpha-synuclein rat model of Parkinson's disease. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:17510-17515.
54. Lundblad M., Andersson M., Winkler C., Kirik D., Wierup N., Cenci M.A. Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson's disease. Eur. J. Neurosci. 2002, 15:120-132.
55. Lundblad M., Decressac M., Mattsson B., Bjorklund A. Impaired neurotransmission caused by overexpression of alpha-synuclein in nigral dopamine neurons. Proc. Natl. Acad. Sci. U. S. A. 2012, 109:3213-3219.
56. Maeda T., Kannari K., Shen H., Arai A., Tomiyama M., Matsunaga M., Suda T. Rapid induction of serotonergic hyperinnervation in the adult rat striatum with extensive dopaminergic denervation. Neurosci. Lett. 2003, 343:17-20.
57. Magen I., Chesselet M.F. Genetic mouse models of Parkinson's disease: the state of the art. Prog. Brain Res. 2010, 184:53-87.
58. Maia S., Arlicot N., Vierron E., Bodard S., Vergote J., Guilloteau D., Chalon S. Longitudinal and parallel monitoring of neuroinflammation and neurodegeneration in a 6-hydroxydopamine rat model of Parkinson's disease. Synapse 2012, 66:573-583.
59. Maingay M., Romero-Ramos M., Carta M., Kirik D. Ventral tegmental area dopamine neurons are resistant to human mutant alpha-synuclein overexpression. Neurobiol. Dis. 2006, 23:522-532.
60. Manfredsson F.P., Burger C., Sullivan L.F., Muzyczka N., Lewin A.S., Mandel R.J. rAAV-Mediated nigral human parkin over-expression partially ameliorates motor deficits via enhanced dopamine neurotransmission in a rat model of Parkinson's disease. Exp. Neurol. 2007, 207:289-301.
61. Mann D.M., Yates P.O. Pathological basis for neurotransmitter changes in Parkinson's disease. Neuropathol. Appl. Neurobiol. 1983, 9:3-19.
62. Marsden C.D. Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 1994, 57:672-681.
63. McFarland N.R., Fan Z., Xu K., Schwarzschild M.A., Feany M.B., Hyman B.T., McLean P.J. Alpha-synuclein S129 phosphorylation mutants do not alter nigrostriatal toxicity in a rat model of Parkinson disease. J. Neuropathol. Exp. Neurol. 2009, 68:515-524.
64. McGeer P.L., McGeer E.G. Inflammation and neurodegeneration in Parkinson's disease. Parkinsonism Relat. Disord. 2004, 10(Suppl. 1):S3-S7.
65. Neumann M., Kahle P.J., Giasson B.I., Ozmen L., Borroni E., Spooren W., Muller V., Odoy S., Fujiwara H., Hasegawa M., Iwatsubo T., Trojanowski J.Q., Kretzschmar H.A., Haass C. Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies. J. Clin. Invest. 2002, 110:1429-1439.
66. Nutt J.G., Burchiel K.J., Comella C.L., Jankovic J., Lang A.E., Laws E.R., Lozano A.M., Penn R.D., Simpson R.K., Stacy M., Wooten G.F. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology 2003, 60:69-73.
67. Olsson M., Nikkhah G., Bentlage C., Bjorklund A. Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test. J. Neurosci. 1995, 15:3863-3875.
68. Patt S., Gerhard L. A Golgi study of human locus coeruleus in normal brains and in Parkinson's disease. Neuropathol. Appl. Neurobiol. 1993, 19:519-523.
69. Reader T.A., Gauthier P. Catecholamines and serotonin in the rat central nervous system after 6-OHDA, 5-7-DHT and p-CPA. J. Neural Transm. 1984, 59:207-227.
70. Recchia A., Rota D., Debetto P., Peroni D., Guidolin D., Negro A., Skaper S.D., Giusti P. Generation of a alpha-synuclein-based rat model of Parkinson's disease. Neurobiol. Dis. 2008, 30:8-18.
71. Reeve A.K., Park T.K., Jaros E., Campbell G.R., Lax N.Z., Hepplewhite P.D., Krishnan K.J., Elson J.L., Morris C.M., McKeith I.G., Turnbull D.M. Relationship between mitochondria and alpha-synuclein: a study of single substantia nigra neurons. Arch. Neurol. 2012, 69:385-393.
72. Rosenblad C., Kirik D., Devaux B., Moffat B., Phillips H.S., Bjorklund A. Protection and regeneration of nigral dopaminergic neurons by neurturin or GDNF in a partial lesion model of Parkinson's disease after administration into the striatum or the lateral ventricle. Eur. J. Neurosci. 1999, 11:1554-1566.
73. Ryu E.J., Harding H.P., Angelastro J.M., Vitolo O.V., Ron D., Greene L.A. Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson's disease. J. Neurosci. 2002, 22:10690-10698.
74. Sauer H., Oertel W.H. Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde tracing and immunocytochemical study in the rat. Neuroscience 1994, 59:401-415.
75. Scatton B., Javoy-Agid F., Rouquier L., Dubois B., Agid Y. Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson's disease. Brain Res. 1983, 275:321-328.
76. Schallert T., Fleming S.M., Leasure J.L., Tillerson J.L., Bland S.T. CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, Parkinsonism and spinal cord injury. Neuropharmacology 2000, 39:777-787.
77. Schapira A.H. Mitochondrial pathology in Parkinson's disease. Mt. Sinai J. Med. 2011, 78:872-881.
78. Schwarting R.K., Huston J.P. The unilateral 6-hydroxydopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery and treatments. Prog. Neurobiol. 1996, 50:275-331.
79. Sotiriou E., Vassilatis D.K., Vila M., Stefanis L. Selective noradrenergic vulnerability in alpha-synuclein transgenic mice. Neurobiol. Aging 2010, 31:2103-2114.
80. Spillantini M.G., Schmidt M.L., Lee V.M., Trojanowski J.Q., Jakes R., Goedert M. Alpha-synuclein in Lewy bodies. Nature 1997, 388:839-840.
81. St Martin J.L., Klucken J., Outeiro T.F., Nguyen P., Keller-McGandy C., Cantuti-Castelvetri I., Grammatopoulos T.N., Standaert D.G., Hyman B.T., McLean P.J. Dopaminergic neuron loss and up-regulation of chaperone protein mRNA induced by targeted over-expression of alpha-synuclein in mouse substantia nigra. J. Neurochem. 2007, 100:1449-1457.
82. Strome E.M., Zis A.P., Doudet D.J. Electroconvulsive shock enhances striatal dopamine D1 and D3 receptor binding and improves motor performance in 6-OHDA-lesioned rats. J. Psychiatry Neurosci. 2007, 32:193-202.
83. Theodore S., Cao S., McLean P.J., Standaert D.G. Targeted overexpression of human alpha-synuclein triggers microglial activation and an adaptive immune response in a mouse model of Parkinson disease. J. Neuropathol. Exp. Neurol. 2008, 67:1149-1158.
84. Ulusoy A., Decressac M., Kirik D., Bjorklund A. Viral vector-mediated overexpression of alpha-synuclein as a progressive model of Parkinson's disease. Prog. Brain Res. 2010, 184:89-111.
85. Unger E.L., Eve D.J., Perez X.A., Reichenbach D.K., Xu Y., Lee M.K., Andrews A.M. Locomotor hyperactivity and alterations in dopamine neurotransmission are associated with overexpression of A53T mutant human alpha-synuclein in mice. Neurobiol. Dis. 2006, 21:431-443.
86. Ungerstedt U. 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur. J. Pharmacol. 1968, 5:107-110.
87. van der Putten H., Wiederhold K.H., Probst A., Barbieri S., Mistl C., Danner S., Kauffmann S., Hofele K., Spooren W.P., Ruegg M.A., Lin S., Caroni P., Sommer B., Tolnay M., Bilbe G. Neuropathology in mice expressing human alpha-synuclein. J. Neurosci. 2000, 20:6021-6029.
88. Vercammen L., Van der Perren A., Vaudano E., Gijsbers R., Debyser Z., Van den Haute C., Baekelandt V. Parkin protects against neurotoxicity in the 6-hydroxydopamine rat model for Parkinson's disease. Mol. Ther. 2006, 14:716-723.
89. Walsh S., Finn D.P., Dowd E. Time-course of nigrostriatal neurodegeneration and neuroinflammation in the 6-hydroxydopamine-induced axonal and terminal lesion models of Parkinson's disease in the rat. Neuroscience 2011, 175:251-261.
90. Winkler C., Kirik D., Bjorklund A., Cenci M.A. l-DOPA-induced dyskinesia in the intrastriatal 6-hydroxydopamine model of Parkinson's disease: relation to motor and cellular parameters of nigrostriatal function. Neurobiol. Dis. 2002, 10:165-186.
91. Xie W., Chung K.K. alpha-Synuclein impairs normal dynamics of mitochondria in cell and animal models of Parkinson's disease. J. Neurochem. 2012, in press.
92. Yamada M., Iwatsubo T., Mizuno Y., Mochizuki H. Overexpression of alpha-synuclein in rat substantia nigra results in loss of dopaminergic neurons, phosphorylation of alpha-synuclein and activation of caspase-9: resemblance to pathogenetic changes in Parkinson's disease. J. Neurochem. 2004, 91:451-461.
93. Yamada M., Mizuno Y., Mochizuki H. Parkin gene therapy for alpha-synucleinopathy: a rat model of Parkinson's disease. Hum. Gene Ther. 2005, 16:262-270.
94. Zarow C., Lyness S.A., Mortimer J.A., Chui H.C. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch. Neurol. 2003, 60:337-341.
95. Zhou F.C., Bledsoe S., Murphy J. Serotonergic sprouting is induced by dopamine-lesion in substantia nigra of adult rat brain. Brain Res. 1991, 556:108-116.