NM  Vol.4 No.4 , December 2013
Involvement of CRH Receptors in the Neuroprotective Action of R-Apomorphine in the Striatal 6-OHDA Rat Model
ABSTRACT

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-hydroxydopamine rat model. The expression of 84 genes was analysed by using the rat neurotrophins and receptors RT2 ProfilerTM 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 involved 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.


Cite this paper
M. Varçin, E. Bentea, S. Roosens, Y. Michotte and S. Sarre, "Involvement of CRH Receptors in the Neuroprotective Action of R-Apomorphine in the Striatal 6-OHDA Rat Model," Neuroscience and Medicine, Vol. 4 No. 4, 2013, pp. 299-318. doi: 10.4236/nm.2013.44044.
References
[1]   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

[2]   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

[3]   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

[4]   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

[5]   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

[6]   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

[7]   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

[8]   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

[9]   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

[10]   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<612::AID-MDS1010>3.0.CO;2-6

[11]   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

[12]   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

[13]   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

[14]   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

[15]   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

[16]   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

[17]   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

[18]   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

[19]   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.

[20]   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

[21]   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

[22]   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

[23]   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.

[24]   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

[25]   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

[26]   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

[27]   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

[28]   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

[29]   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

[30]   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

[31]   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

[32]   G. Paxinos and C. Watson, “The Rat Brain in Stereotaxic Coordinates,” 2nd Edition, Academic Press, Waltham, 1986.

[33]   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

[34]   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

[35]   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

[36]   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

[37]   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

[38]   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

[39]   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

[40]   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

[41]   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

[42]   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

[43]   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

[44]   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

[45]   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

[46]   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.

[47]   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

[48]   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

[49]   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

[50]   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

[51]   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.

[52]   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

[53]   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

[54]   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

[55]   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

[56]   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

[57]   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

[58]   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

[59]   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

[60]   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

[61]   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.

[62]   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

[63]   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

[64]   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

[65]   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

[66]   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

[67]   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

[68]   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

[69]   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

[70]   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

[71]   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

 
 
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