Time-course behavioral features are correlated with Parkinson's disease‑associated pathology in a 6-hydroxydopamine hemiparkinsonian rat model

Su,Rui‑Jun; Zhen,Jun‑Li; Wang,Wei; Zhang,Jian‑Liang; Zheng,Yan; Wang,Xiao‑Min

doi:10.3892/mmr.2017.8277

Time-course behavioral features are correlated with Parkinson's disease‑associated pathology in a 6-hydroxydopamine hemiparkinsonian rat model

Authors:
- Rui‑Jun Su
- Jun‑Li Zhen
- Wei Wang
- Jian‑Liang Zhang
- Yan Zheng
- Xiao‑Min Wang
View Affiliations

Affiliations: Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China, Key Laboratory for Neurodegenerative Disorders of The Ministry of Education, Capital Medical University, Beijing 100069, P.R. China
Published online on: December 13, 2017 https://doi.org/10.3892/mmr.2017.8277
Pages: 3356-3363
Copyright: © Su et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. For decades, the unilateral 6‑hydroxydopamine (6‑OHDA) rat model has been employed to investigate the pathogenesis and therapy of PD. However, the behavior and associated pathological features of the model long term have not previously been described dynamically. In the present study, the unilateral model was established by 6‑OHDA injection in the striatum. The PD rat model was determined 2 weeks following surgery, according to the apomorphine (APO)‑induced rotations, cylinder, rotarod and open field tests. TH‑positive neurons and fibers in the substantia nigra pars compacta (SNpc) and striatum, respectively, and glial activation in the SNpc, determined by glial fibrillary acidic protein (GFAP) expression for astrocytes and CD11b (Mac1) expression for microglia, were detected by immunohistological staining. Correlation analysis was performed to understand the association between PD‑associated behavior and pathology. The behavioral impairment progressively deteriorated during the process of experiment. In addition, the decrease in TH‑positive neurons was associated with an increase in GFAP‑ and Mac1‑positive cells in the SNpc. Linear regression analysis indicated the association between behavioral and pathological changes. The results of the present study indicate that the APO‑induced rotation, cylinder and rotarod tests are all sensitive and reliable strategies to predict the loss of TH+ neurons. These results provide a potential intervention time‑point and a comprehensive evaluation index system for assessment of PD therapeutic strategies using the hemiparkinsonian rat.

View Figures

View References

1	Redgrave P, Vautrelle N and Reynolds JN: Functional properties of the basal ganglia's re-entrant loop architecture: Selection and reinforcement. Neuroscience. 198:138–151. 2011. View Article : Google Scholar : PubMed/NCBI
2	Su X and Federoff HJ: Immune responses in Parkinson's disease: Interplay between central and peripheral immune systems. Biomed Res Int. 2014:2751782014. View Article : Google Scholar : PubMed/NCBI
3	Jackson-Lewis V, Blesa J and Przedborski S: Animal models of Parkinson's disease. Parkinsonism Relat Disord. 18 Suppl 1:S183–S185. 2012. View Article : Google Scholar : PubMed/NCBI
4	Ungerstedt U: 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol. 5:107–110. 1968. View Article : Google Scholar : PubMed/NCBI
5	Blandini F, Armentero MT and Martignoni E: The 6-hydroxydopamine model: News from the past. Parkinsonism Relat Disord. 14 Suppl 2:S124–S129. 2008. View Article : Google Scholar : PubMed/NCBI
6	Lee CS, Sauer H and Bjorklund A: Dopaminergic neuronal degeneration and motor impairments following axon terminal lesion by instrastriatal 6-hydroxydopamine in the rat. Neuroscience. 72:641–653. 1996. View Article : Google Scholar : PubMed/NCBI
7	Bové J and Perier C: Neurotoxin-based models of Parkinson's disease. Neuroscience. 211:51–76. 2012. View Article : Google Scholar : PubMed/NCBI
8	Meredith GE and Kang UJ: Behavioral models of Parkinson's disease in rodents: A new look at an old problem. Mov Disord. 21:1595–1606. 2006. View Article : Google Scholar : PubMed/NCBI
9	Paxinos G and Watson C: The Rat Brain in Stereotaxic Coordinates. Academic Press; 2005
10	Przedborski S, Levivier M, Jiang H, Ferreira M, Jacksonlewis V, Donaldson D and Togasaki DM: Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by intrastriatal injection of 6-hydroxydopamine. Neuroscience. 67:631–647. 1995. View Article : Google Scholar : PubMed/NCBI
11	Monville C, Torres EM and Dunnett SB: Comparison of incremental and accelerating protocols of the rotarod test for the assessment of motor deficits in the 6-OHDA model. J Neurosci Methods. 158:219–223. 2006. View Article : Google Scholar : PubMed/NCBI
12	Landers MR, Kinney JW and van Breukelen F: Forced exercise before or after induction of 6-OHDA-mediated nigrostriatal insult does not mitigate behavioral asymmetry in a hemiparkinsonian rat model. Brain Res. 1543:263–270. 2014. View Article : Google Scholar : PubMed/NCBI
13	Yuan HL, Li B, Xu J, Wang Y, He Y, Zheng Y and Wang XM: Tenuigenin protects dopaminergic neurons from inflammation-mediated damage induced by the lipopolysaccharide. CNS Neurosci Ther. 18:584–590. 2012. View Article : Google Scholar : PubMed/NCBI
14	van der Perren A, Macchi F, Toelen J, Carlon MS, Maris M, de Loor H, Kuypers DR, Gijsbers R, Van den Haute C, Debyser Z and Baekelandt V: FK506 reduces neuroinflammation and dopaminergic neurodegeneration in an α-synuclein-based rat model for Parkinson's disease. Neurobiol Aging. 36:1559–1568. 2015. View Article : Google Scholar : PubMed/NCBI
15	Sanchez-Guajardo V, Febbraro F, Kirik D and Romero-Ramos M: Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease. PLoS One. 5:e87842010. View Article : Google Scholar : PubMed/NCBI
16	McGeer PL and McGeer EG: Glial reactions in Parkinson's disease. Mov Disord. 23:474–483. 2008. View Article : Google Scholar : PubMed/NCBI
17	Mendez JS and Finn BW: Use of 6-hydroxydopamine to create lesions in catecholamine neurons in rats. Neurosurg. 42:166–173. 1975. View Article : Google Scholar
18	Stott SR and Barker RA: Time course of dopamine neuron loss and glial response in the 6-OHDA striatal mouse model of Parkinson's disease. Eur J Neurosci. 39:1042–1056. 2014. View Article : Google Scholar : PubMed/NCBI
19	Schlachetzki JC, Marxreiter F, Regensburger M, Kulinich A, Winner B and Winkler J: Increased tyrosine hydroxylase expression accompanied by glial changes within the non-lesioned hemisphere in the 6-hydroxydopamine model of Parkinson's disease. Restor Neurol Neurosci. 32:447–462. 2014.PubMed/NCBI
20	Walsh S, Finn DP and 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. 175:251–261. 2011. View Article : Google Scholar : PubMed/NCBI
21	Sauer H and Oertel WH: Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: A combined retrograde tracing and immunocytochemical study in the rat. Neuroscience. 59:401–415. 1994. View Article : Google Scholar : PubMed/NCBI
22	Marti MJ, Saura J, Burke RE, Jackson-Lewis V, Jiménez A, Bonastre M and Tolosa E: Striatal 6-hydroxydopamine induces apoptosis of nigral neurons in the adult rat. Brain Res. 958:185–191. 2002. View Article : Google Scholar : PubMed/NCBI
23	Marti MJ, James CJ, Oo TF, Kelly WJ and Burke RE: Early developmental destruction of terminals in the striatal target induces apoptosis in dopamine neurons of the substantia nigra. J Neurosci. 17:2030–2039. 1997.PubMed/NCBI
24	Prut L and Belzung C: The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: A review. Eur J Pharmacol. 463:3–33. 2003. View Article : Google Scholar : PubMed/NCBI
25	Blandini F, Levandis G, Bazzini E, Nappi G and Armentero MT: Time-course of nigrostriatal damage, basal ganglia metabolic changes and behavioural alterations following intrastriatal injection of 6-hydroxydopamine in the rat: New clues from an old model. Eur J Neurosci. 25:397–405. 2007. View Article : Google Scholar : PubMed/NCBI
26	Mosley RL, Benner EJ, Kadiu I, Thomas M, Boska MD, Hasan K, Laurie C and Gendelman HE: Neuroinflammation, oxidative stress and the pathogenesis of Parkinson's disease. Clin Neurosci Res. 6:261–281. 2006. View Article : Google Scholar : PubMed/NCBI
27	Vivekanantham S, Shah S, Dewji R, Dewji A, Khatri C and Ologunde R: Neuroinflammation in Parkinson's disease: Role in neurodegeneration and tissue repair. Int J Neurosci. 125:717–725. 2015. View Article : Google Scholar : PubMed/NCBI
28	Depino AM, Earl C, Kaczmarczyk E, Ferrari C, Besedovsky H, del Rey A, Pitossi FJ and Oertel WH: Microglial activation with atypical proinflammatory cytokine expression in a rat model of Parkinson's disease. Eur J Neurosci. 18:2731–2742. 2003. View Article : Google Scholar : PubMed/NCBI