Involvement of CRH Receptors in the Neuroprotective Action of R-Apomorphine in the Striatal 6-OHDA Rat Model — Oak Academic Publishing
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Involvement of CRH Receptors in the Neuroprotective Action of R-Apomorphine in the Striatal 6-OHDA Rat Model
Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Faculty of Medicine and Phar-macy, Brussels, Belgium
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Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Faculty of Medicine and Phar-macy, Brussels, Belgium
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Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Faculty of Medicine and Phar-macy, Brussels, Belgium
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Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Faculty of Medicine and Phar-macy, Brussels, Belgium
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Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Faculty of Medicine and Phar-macy, Brussels, Belgium; Belgian Pharmacists Association, Medicines Control Laboratory, Brussels, Belgium
1 Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Faculty of Medicine and Phar-macy, Brussels, Belgium
2 Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Faculty of Medicine and Phar-macy, Brussels, Belgium
3 Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Faculty of Medicine and Phar-macy, Brussels, Belgium
4 Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Faculty of Medicine and Phar-macy, Brussels, Belgium
5 Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Faculty of Medicine and Phar-macy, Brussels, Belgium; Belgian Pharmacists Association, Medicines Control Laboratory, Brussels, Belgium
The dopamine D1-D2 receptor agonist , R-apomorphine , has been shown to be neuroprotective in different models of Parkinson’s disease. Different mechanisms of action for this effect have been proposed, but not verified in the striatal 6-hydroxydopamine rat model. In this study, the expression of a set of genes involved in 1) signaling, 2) growth and differentiation, 3) neuronal regeneration and survival, 4) apoptosis and 5) inflammation in the striatum was measured after a subchronic R-apomorphine treatment (10 mg/kg/day, subcutaneously, during 11 days) in the striatal 6-hydroxy dopamine rat model. The expression of 84 genes was analysed by using the rat neurotrophins and receptors RT 2 Profiler TM PCR array. The neuroprotective effects of R-apomorphine in the striatal 6-hydroxydopamine model were confirmed by neurochemical and behavioural analysis. The expression data suggest the observed neuroprotection involve d the alteration of the gene and the protein expression levels of the anti-inflammatory corticotropin releasing hormone receptor ( CRHR) 1 and the pro-inflammatory CRHR2 receptor confirming its potential anti-inflammatory action .
KeywordsApomorphineGene ExpressionInflammationNeuroprotectionParkinson’s DiseaseStriatal 6-Hydroxydopamine Rat Model
A. H. Schapira, “Neurobiology and Treatment of Parkinson’s Disease,” Trends in Pharmacological Sciences, Vol. 30, No. 1, 2009, pp. 41-47. http://dx.doi.org/10.1016/j.tips.2008.10.005
M. B. Youdim, W. J. Geldenhuys and C. J. Van der Schyf, “Why Should We Use Multifunctional Neuroprotective and Neurorestorative Drugs for Parkinson’s Disease?” Parkinsonism & Related Disorders, Vol. 13, No. Suppl 3, 2007, pp. S281-S291. http://dx.doi.org/10.1016/S1353-8020(08)70017-8
P. A. LeWitt, “Subcutaneously Administered Apomorphine: Pharmacokinetics and Metabolism,” Neurology, Vol. 62, No. 6, 2004, pp. S8-S11. http://dx.doi.org/10.1212/WNL.62.6_suppl_4.S8
I. U. Haq, P. A. Lewitt and H. H. Fernandez, “Apomorphine Therapy in Parkinson’s Disease: A Review,” Expert Opinion on Pharmacotherapy, Vol. 8, No. 16, 2007, pp. 2799-2809. http://dx.doi.org/10.1517/14656566.8.16.2799
P. A. LeWitt, et al., “Open-Label Study Assessment of Safety and Adverse Effects of Subcutaneous Apomorphine Injections in Treating ‘off’ Episodes in Advanced Parkinson Disease,” Clinical Neuropharmacology, Vol. 32, No. 2, 2009, pp. 89-93. http://dx.doi.org/10.1097/WNF.0b013e31816d91f9
F. Stocchi, “Use of Apomorphine in Parkinson’s Disease,” Neurological Sciences, Vol. 29, No. Suppl 5, 2008, pp. S383-S386. http://dx.doi.org/10.1007/s10072-008-1053-8
M. Kyriazis, “Neuroprotective, Anti-Apoptotic Effects of Apomorphine,” Journal of Anti-Aging Medicine, Vol. 6, No. 1, 2003, pp. 21-28. http://dx.doi.org/10.1089/109454503765361551
S. Ribaric, “The Pharmacological Properties and Therapeutic Use of Apomorphine,” Molecules, Vol. 17, No. 5, 2012, pp. 5289-5309. http://dx.doi.org/10.3390/molecules17055289
E. Grunblatt, et al., “Gene Expression Analysis in Nmethyl-4-phenyl-1,2,3,6-tetrahydropyridine Mice Model of Parkinson’s Disease Using cDNA Microarray: Effect of R-Apomorphine,” Journal of Neurochemistry, Vol. 78, No. 1, 2001, pp. 1-12. http://dx.doi.org/10.1046/j.1471-4159.2001.00397.x
E. Grunblatt, et al., “Apomorphine Protects against MPTP-Induced Neurotoxicity in Mice,” Movement Disorders, Vol. 14, No. 4, 1999, pp. 612-618. http://dx.doi.org/10.1002/1531-8257(199907)14:4 3.0.CO;2-6
G. Battaglia, et al., “Continuous Subcutaneous Infusion of Apomorphine Rescues Nigro-Striatal Dopaminergic Terminals Following MPTP Injection in Mice,” Neuropharmacology, Vol. 42, No. 3, 2002, pp. 367-373. http://dx.doi.org/10.1016/S0028-3908(01)00178-2
G. Battaglia, et al., “Morphological and Biochemical Evidence That Apomorphine Rescues Striatal Dopamine Terminals and Prevents Methamphetamine Toxicity,” Annals of the New York Academy of Sciences, Vol. 965, 2002, pp. 254-266. http://dx.doi.org/10.1111/j.1749-6632.2002.tb04167.x
E. E. Sam and N. Verbeke, “Free Radical Scavenging Properties of Apomorphine Enantiomers and Dopamine: Possible Implication in Their Mechanism of Action in Parkinsonism,” Journal of Neural Transmission Parkinson’s Disease and Dementia Section, Vol. 10, No. 2-3, 1995, pp. 115-27. http://dx.doi.org/10.1007/BF02251227
H. Yuan, et al., “Neuroprotective and Neurotrophic Effect of Apomorphine in the Striatal 6-OHDA-Lesion Rat Model of Parkinson’s Disease,” Brain Research, Vol. 1026, No. 1, 2004, pp. 95-107. http://dx.doi.org/10.1016/j.brainres.2004.08.015
Y. K. Chen, et al., “Potent, Hydroxyl Radical-Scavenging Effect of Apomorphine with Iron and Dopamine Perfusion in Rat Striatum,” Brain Research, Vol. 896, No. 1-2, 2001, pp. 165-168. http://dx.doi.org/10.1016/S0006-8993(01)02081-9
F. Fornai, et al., “Dose-Dependent Protective Effects of Apomorphine against Methamphetamine-Induced Nigrostriatal Damage,” Brain Research, Vol. 898, No. 1, 2001, pp. 27-35. http://dx.doi.org/10.1016/S0006-8993(01)02125-4
E. Himeno, et al., “Apomorphine Treatment in Alzheimer Mice Promoting Amyloid-Beta Degradation,” Annals of Neurology, Vol. 69, No. 2, 2011, pp. 248-256. http://dx.doi.org/10.1002/ana.22319
M. Gassen, et al., “Apomorphine Is a Highly Potent Free Radical Scavenger in Rat Brain Mitochondrial Fraction,” European Journal of Pharmacology, Vol. 308, No. 2, 1996, pp. 219-225. http://dx.doi.org/10.1016/0014-2999(96)00291-9
G. Williamson, K. Faulkner and G. W. Plumb, “Glucosinolates and Phenolics as Antioxidants from Plant Foods,” European Journal of Cancer Prevention, Vol. 7, No. 1, 1998, pp. 17-21.
A. Ubeda, et al., “Iron-Reducing and Free-RadicalScavenging Properties of Apomorphine and Some Related Benzylisoquinolines,” Free Radical Biology & Medicine, Vol. 15, No. 2, 1993, pp. 159-167. http://dx.doi.org/10.1016/0891-5849(93)90055-Y
H. Hara, M. Ohta and T. Adachi, “Apomorphine Protects against 6-Hydroxydopamine-Induced Neuronal Cell Death through Activation of the Nrf2-ARE Pathway,” Journal of Neuroscience Research, Vol. 84, No. 4, 2006, pp. 860-866. http://dx.doi.org/10.1002/jnr.20974
E. Grunblatt, et al., “Effects of R- and S-Apomorphine on MPTP-Induced Nigro-Striatal Dopamine Neuronal Loss,” Journal of Neurochemistry, Vol. 77, No. 1, 2001, pp. 146-156. http://dx.doi.org/10.1046/j.1471-4159.2001.t01-1-00227.x
L. Ma, et al., “Activation of Glutathione Peroxidase and Inhibition of p53-Related Apoptosis by Apomorphine,” Journal of Alzheimer’s Disease, Vol. 27, No. 1, 2011, pp. 225-237.
O. Weinreb, S. Mandel and M. B. Youdim, “Gene and Protein Expression Profiles of Antiand Pro-Apoptotic Actions of Dopamine, R-Apomorphine, Green Tea Polyphenol (-)-Epigallocatechine-3-Gallate, and Melatonin,” Annals of the New York Academy of Sciences, Vol. 993, No. , 2003, pp. 351-361; Discussion 387-393. http://dx.doi.org/10.1111/j.1749-6632.2003.tb07544.x
V. Coronas, et al., “Dopamine D3 Receptor Stimulation Promotes the Proliferation of Cells Derived from the Post-Natal Subventricular Zone,” Journal of Neurochemistry, Vol. 91, No. 6, 2004, pp. 1292-1301. http://dx.doi.org/10.1111/j.1471-4159.2004.02823.x
A. Li, et al., “Apomorphine-Induced Activation of Dopamine Receptors Modulates FGF-2 Expression in Astrocytic Cultures and Promotes Survival of Dopaminergic Neurons,” FASEB Journal, Vol. 20, No. 8, 2006, pp. 1263-1265. http://dx.doi.org/10.1096/fj.05-5510fje
H. Guo, et al., “Apomorphine Induces Trophic Factors That Support Fetal Rat Mesencephalic Dopaminergic Neurons in Cultures,” European Journal of Neuroscience, Vol. 16, No. 10, 2002, pp. 1861-1870. http://dx.doi.org/10.1046/j.1460-9568.2002.02256.x
M. Roceri, et al., “Stimulatory Role of Dopamine on Fibroblast Growth Factor-2 Expression in Rat Striatum,” Journal of Neurochemistry, Vol. 76, No. 4, 2001, pp. 990-997. http://dx.doi.org/10.1046/j.1471-4159.2001.00088.x
F. Vaglini, et al., “Apomorphine Offers New Insight into Dopaminergic Neuron Vulnerability in Mesencephalic Cultures,” Neuropharmacology, Vol. 55, No. 5, 2008, pp. 737-742. http://dx.doi.org/10.1016/j.neuropharm.2008.06.041
M. Varcin, et al., “Acute versus Long-Term Effects of 6-Hydroxydopamine on Oxidative Stress and Dopamine Depletion in the Striatum of Mice,” Journal Of Neuroscience Methods, Vol. 202, No. 2, 2011, pp. 128-136. http://dx.doi.org/10.1016/j.jneumeth.2011.07.004
S. Taylor, et al., “A Practical Approach to RT-qPCR-Publishing Data That Conform to the MIQE Guidelines,” Methods, Vol. 50, No. 4, 2010, pp. S1-S5. http://dx.doi.org/10.1016/j.ymeth.2010.01.005
G. Paxinos and C. Watson, “The Rat Brain in Stereotaxic Coordinates,” 2nd Edition, Academic Press, Waltham, 1986.
M. J. Millan, et al., “The Role of Dopamine D3 Compared with D2 Receptors in the Control of Locomotor Activity: A Combined Behavioural and Neurochemical Analysis with Novel, Selective Antagonists in Rats,” Psychopharmacology (Berlin), Vol. 174, No. 3, 2004, pp. 341-357. http://dx.doi.org/10.1007/s00213-003-1770-x
B. Winner, et al., “Dopamine Receptor Activation Promotes Adult Neurogenesis in an Acute Parkinson Model,” Experimental Neurology, Vol. 219, No. 2, 2009, pp. 543-552. http://dx.doi.org/10.1016/j.expneurol.2009.07.013
S. Mandel, O. Weinreb and M. B. Youdim, “Using cDNA Microarray to Assess Parkinson’s Disease Models and the Effects of Neuroprotective Drugs,” Trends in Pharmacological Sciences, Vol. 24, No. 4, 2003, pp. 184-191. http://dx.doi.org/10.1016/S0165-6147(03)00067-1
A. S. Adewale, H. Macarthur and T. C. Westfall, “Neuropeptide Y Induced Modulation of Dopamine Synthesis in the Striatum,” Regulatory Peptides, Vol. 129, No. 1-3, 2005, pp. 73-78. http://dx.doi.org/10.1016/j.regpep.2005.01.005
S. J. Na, A. G. DiLella, E. V. Lis, K. Jones, D. M. Levine, D. J. Stone and J. F. Hess, “Molecular Profiling of a 6-Hydroxydopamine Model of Parkinson’s Disease,” Neurochemical Research, Vol. 35, No. 5, 2010, pp. 761-772. http://dx.doi.org/10.1007/s11064-010-0133-3
L. Marinova-Mutafchieva, M. Sadeghian, L. Broom, J. B. Davis, A. D. Medhurst and D. T. Dexter, “Relationship between Microglial Activation and Dopaminergic Neuronal Loss in the Substantia Nigra: A Time Course Study in a 6-Hydroxydopamine Model of Parkinson’s Disease,” Journal of Neurochemistry, Vol. 110, No. 3, 2009, pp. 966-975. http://dx.doi.org/10.1111/j.1471-4159.2009.06189.x
S. Walsh, D. P. Finn and E. Dowd, “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, Vol. 175, 2009, pp. 251-261. http://dx.doi.org/10.1016/j.neuroscience.2010.12.005
L. M. Collins, A. Toulouse, T. J. Connor and Y. M. Nolan, “Contributions of Central and Systemic Inflammation to the Pathophysiology of Parkinson’s Disease,” Neuropharmacology, Vol. 62, No. 7, 2012, pp. 2154-2168. http://dx.doi.org/10.1016/j.neuropharm.2012.01.028
V. A. Doze and D. M. Perez, “G-Protein-Coupled Receptors in Adult Neurogenesis,” Pharmacological Reviews, Vol. 64, No. 3, 2012, pp. 645-675. http://dx.doi.org/10.1124/pr.111.004762
J. Ock, H. Lee, S. Kim, W. H. Lee, D. K. Choi, E. J. Park, S. H. Kim, I. K. Kim and K. Suk, “Induction of Microglial Apoptosis by Corticotropin-Releasing Hormone,” Journal of Neurochemistry, Vol. 98, No. 3, 2006, pp. 962-972. http://dx.doi.org/10.1111/j.1471-4159.2006.03933.x
A. Abuirmeileh, A. Harkavyi, A. Kingsbury, R. Lever and P. S. Whitton, “The CRF-Like Peptide Urocortin Greatly Attenuates Loss of Extracellular Striatal Dopamine in Rat Models of Parkinson’s Disease by Activating CRF(1) Receptors,” European Journal of Pharmacology, Vol. 604, No. 1-3, 2009, pp. 45-50. http://dx.doi.org/10.1016/j.ejphar.2008.11.009
A. Abuirmeileh, A. Harkavyi, R. Lever, C. S. Biggs and P. S. Whitton, “Urocortin, a CRF-Like Peptide, Restores Key Indicators of Damage in the Substantia Nigra in a Neuroinflammatory Model of Parkinson’s Disease,” Journal of Neuroinflammation, Vol. 4, 2007, p. 19. http://dx.doi.org/10.1186/1742-2094-4-19
A. Abuirmeileh, R. Lever, A. E. Kingsbury, A. J. Lees, I. C. Locke, R. A. Knight, H. S. Chowdrey, C. S. Biggs and P. S. Whitton, “The Corticotrophin-Releasing Factor-Like Peptide Urocortin Reverses Key Deficits in Two Rodent Models of Parkinson’s Disease,” European Journal of Neuroscience, Vol. 26, No. 2, 2007, pp. 417-423. http://dx.doi.org/10.1111/j.1460-9568.2007.05653.x
W. A. Pedersen, R. Wan, P. Zhang and M. P. Mattson, “Urocortin, but not Urocortin II, Protects Cultured Hippocampal Neurons from Oxidative and Excitotoxic Cell Death via Corticotropin-Releasing Hormone Receptor Type I,” Journal of Neuroscience, Vol. 22, No. 2, 2002, pp. 404-412.
E. Gonzalez-Rey, A. Fernandez-Martin, A. Chorny and M. Delgado, “Therapeutic Effect of Urocortin and Adrenomedullin in a Murine Model of Crohn’s Disease,” Gut, Vol. 55, No. 6, 2006, pp. 824-832. http://dx.doi.org/10.1136/gut.2005.084525
H. Y. Huang, S. Z. Lin, W. F. Chen, K. W. Li, J. S. Kuo and M. J. Wang, “Urocortin Modulates Dopaminergic Neuronal Survival via Inhibition of Glycogen Synthase Kinase-3β and Histone Deacetylase,” Neurobiology of Aging, Vol. 32, No. 9, 2011, pp. 1662-1677. http://dx.doi.org/10.1016/j.neurobiolaging.2009.09.010
Y. Kim, M. K. Park and S. Chung, “Protective Effect of Urocortin on 1-Methyl-4-Phenylpyridinium-Induced Dopaminergic Neuronal Death,” Molecules and Cells, Vol. 30, No. 5, 2010, pp. 427-433. http://dx.doi.org/10.1007/s10059-010-0132-x
A. C. Moss, P. Anton, T. Savidge, et al., “Urocortin II Mediates Pro-Inflammatory Effects in Human Colonocytes via Corticotropin-Releasing Hormone Receptor 2α,” Gut, Vol. 56, No. 9, 2007, pp. 1210-1217. http://dx.doi.org/10.1136/gut.2006.110668
E. Kokkotou, D. Torres, A. C. Moss, M. O'Brien, D. E. Grigoriadis, K. Karalis and C. Pothoulakis, “Corticotropin-Releasing Hormone Receptor 2-Deficient Mice Have Reduced Intestinal Inflammatory Responses,” Journal of Immunology, Vol. 177, No. 5, 2006, pp. 3355-3361.
M. Decressac, L. Prestoz, J. Veran, A. Cantereau, M. Jaber and A. Gaillard, “Neuropeptide Y Stimulates Proliferation, Migration and Differentiation of Neural Precursors from the Subventricular Zone in Adult Mice,” Neurobiology of Disease, Vol. 34, No. 3, 2009, pp. 441-449. http://dx.doi.org/10.1016/j.nbd.2009.02.017
M. Dimitrijevic, S. Stanojevica, K. Mitica, N. Kustrimovica, V. Vujicb, T. Miletica and V. Kovacevic-Jovanovica, “The Anti-Inflammatory Effect of Neuropeptide Y (NPY) in Rats Is Dependent on Dipeptidyl Peptidase 4 (DP4) Activity and Age,” Peptides, Vol. 29, No. 12, 2008, pp. 2179-2187. http://dx.doi.org/10.1016/j.peptides.2008.08.017
M. Decressac, B. Wright, B. David, P. Tyers, M. Jaber, R. A. Barker and A. Gaillard, “Exogenous Neuropeptide Y Promotes in Vivo Hippocampal Neurogenesis,” Hippocampus, Vol. 21, No. 3, 2011, pp. 233-238. http://dx.doi.org/10.1002/hipo.20765
N. Thiriet, X. L. Deng, M. Solinas, B. Ladenheim, W. Curtis, S. R. Goldberg, R. D. Palmiter and J. L. Cadet, “Neuropeptide Y Protects against Methamphetamine-Induced Neuronal Apoptosis in the Mouse Striatum,” Journal of Neuroscience, Vol. 25, No. 22 , 2005, pp. 5273-5279. http://dx.doi.org/10.1523/JNEUROSCI.4893-04.2005
A. S. Adewale, H. Macarthur and T. C. Westfall, “Neuropeptide Y-Induced Enhancement of the Evoked Release of Newly Synthesized Dopamine in Rat Striatum: Mediation by Y2 Receptors,” Neuropharmacology, Vol. 52, No. 6, 2007, pp. 1396-1402. http://dx.doi.org/10.1016/j.neuropharm.2007.01.018
D. Quarta, C. P. Leslie, R. Carletti, E. Valerio and L. Caberlotto, “Central Administration of NPY or an NPY-Y5 Selective Agonist Increase in Vivo Extracellular Monoamine Levels in Mesocorticolimbic Projecting Areas,” Neuropharmacology, Vol. 60, No. 2-3, 2011, pp. 328-335. http://dx.doi.org/10.1016/j.neuropharm.2010.09.016
E. Zambello, L. Zanetti, G. F. Hédou, O. Angelici, R. Arban, R. O. Tasan, G. Sperk and L. Caberlotto, “Neuropeptide Y-Y2 Receptor knockout Mice: Influence of Genetic Background on Anxiety-Related Behaviors,” Neuroscience, Vol. 176, No. , 2010, pp. 420-430. http://dx.doi.org/10.1016/j.neuroscience.2010.10.075
M. Smialowska, H. Domin, B. Zieba, E. Kozniewska, R. Michalik, P. Piotrowski and M. Kajta, “Neuroprotective Effects of Neuropeptide Y-Y2 and Y5 Receptor Agonists in Vitro and in Vivo,” Neuropeptides, Vol. 43, No. 3, 2009, pp. 235-249. http://dx.doi.org/10.1016/j.npep.2009.02.002
B. Mertens, A. Massie, Y. Michotte and S. Sarre, “Effect of Nigrostriatal Damage Induced by 6-Hydroxydopamine on the Expression of Glial Cell Line-Derived Neurotrophic Factor in the Striatum of the Rat,” Neuroscience, Vol. 162, No. 1, 2009, pp. 148-154. http://dx.doi.org/10.1016/j.neuroscience.2009.04.036
S. Mandel, E. Grünblatt, P. Riederer and M. B. Youdim, “Genes and Oxidative Stress in Parkinsonism: cDNA Microarray Studies,” Advances in Neurology, Vol. 91, 2003, pp. 123-132.
M. Ohta, I. Mizuta, K. Ohta, M. Nishimura, E. Mizuta, K. Hayashid and S. Kuno, “Apomorphine Up-Regulates NGF and GDNF Synthesis in Cultured Mouse Astrocytes,” Biochemical and Biophysical Research Communications, Vol. 272, No. 1, 2000, pp. 18-22. http://dx.doi.org/10.1006/bbrc.2000.2732
I. Branchi, I. D’Andreaa, M. Armida, et al., “Striatal 6-OHDA Lesion in Mice: Investigating Early Neurochemical Changes Underlying Parkinson’s Disease,” Behavioural Brain Research, Vol. 208, No. 1, 2010, pp. 137-143. http://dx.doi.org/10.1016/j.bbr.2009.11.020
V. Francardo, A. Recchia, N. Popovic, D. Andersson, H. Nissbrandt and M. A. Cenci, “Impact of the Lesion Procedure on the Profiles of Motor Impairment and Molecular Responsiveness to L-DOPA in the 6-Hydroxydopamine Mouse Model of Parkinson’s Disease,” Neurobiology of Disease, Vol. 42, No. 3, 2011, pp. 327-340. http://dx.doi.org/10.1016/j.nbd.2011.01.024
S. J. Haas, A. Ahrens, S. Petrov, O. Schmitt and A. Wree, “Quinolinic Acid Lesions of the Caudate Putamen in the Rat Lead to a Local Increase of Ciliary Neurotrophic Factor,” Journal of Anatomy, Vol. 204, No. 4, 2004, pp. 271-281. http://dx.doi.org/10.1111/j.0021-8782.2004.00279.x
R. W. Rodrigues, V. C. Gomide and G. Chadi, “Astroglial and Microglial Activation in the Wistar Rat Ventral Tegmental Area after a Single Striatal Injection of 6-Hydroxydopamine,” International Journal of Neuroscience, Vol. 114, No. 2, 2004, pp. 197-216. http://dx.doi.org/10.1080/00207450490249338
V. C. Gomide, G. A. Silveira and G. Chadi, “Transient and Widespread Astroglial Activation in the Brain after a Striatal 6-OHDA-Induced Partial Lesion of the Nigrostriatal System,” International Journal of Neuroscience, Vol. 115, No. 1, 2005, pp. 99-117. http://dx.doi.org/10.1080/00207450490512696
J. Henning, U. Strauss, A. Wree, J. Gimsa, A. Rolfs, R. Benecke and U. Gimsa, “Differential Astroglial Activation in 6-Hydroxydopamine Models of Parkinson’s Disease,” Neuroscience Research, Vol. 62, No. 4, 2008, pp. 246-253. http://dx.doi.org/10.1016/j.neures.2008.09.001
M. E. Emborg, “Evaluation of Animal Models of Parkinson’s Disease for Neuroprotective Strategies,” Journal of Neuroscience Methods, Vol. 139, No. 2, 2004, pp. 121-143. http://dx.doi.org/10.1016/j.jneumeth.2004.08.004
F. Blandini, M. T. Armentero and E. Martignoni, “The 6-Hydroxydopamine Model: News from the Past,” Parkinsonism & Related Disorders, Vol. 14, Suppl. 2, 2008, pp. S124-S129. http://dx.doi.org/10.1016/j.parkreldis.2008.04.015
S. Duty and P. Jenner, “Animal Models of Parkinson’s Disease: A Source of Novel Treatments and Clues to the Cause of the Disease,” British Journal of Pharmacology, Vol. 164, No. 4, 2011, pp. 1357-1391. http://dx.doi.org/10.1111/j.1476-5381.2011.01426.x