Induction of Parkinson’s Disease Model in Rat by Rotenone

Document Type : Original Article (s)

Authors

1 MSc Student, Department of Biological Science and Biotechnology, School of Basic Sciences, University of Kurdistan, Sanandaj, Iran

2 Assistant Professor, Department of Biological Science and Biotechnology, School of Basic Sciences, University of Kurdistan, Sanandaj, Iran

3 Assistant Professor, Cellular and Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran

4 Assistant Professor, Department of Physiology and Pharmacology, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

Abstract

Background: Many efforts have been made to find a proper animal model for Parkinson’s disease, in order to improve our knowledge about this disorder and to find therapeutic approaches. Generally, the reproducibility of experiments in laboratory animals is accompanied by some troubles. Therefore, the validity of model is certified via certain behavioral tests. The present study aimed to find an accurate and reproducible rat model of inducing Parkinson’s disease by rotenone.Methods: Male Wistar rats weighting 400 ± 50 g (10-12 months of age) received several doses of rotenone (1, 2, or 3 mg/kg) or its vehicle subcutaneously every 48 hours. Three behavioral tests (rotarod, rearing and bar) were run in order to check the development of model.Findings: Rotenone (2 mg/kg/48h) was an efficient dose beside its low mortality. The latency time of rotarod test and movement skills in rearing test decreased significantly in rotenone (2 mg/kg/48h) treated animals (P < 0.05). In addition, the results of bar test showed the augmentation of catalepsy in rotenone group compared to vehicle-treated animals (P < 0.05). In addition, the statistical correlation between behavioral tests justified the development of movement disorders in the model.Conclusion: According to the results, it was concluded that rotenone (2 mg/kg/48h) was the best approach with reproducible capacity for induction of Parkinson’s disease model.

Keywords


  1. de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol 2006; 5(6): 525-35.
  2. Choi WS, Palmiter RD, Xia Z. Loss of mitochondrial complex I activity potentiates dopamine neuron death induced by microtubule dysfunction in a Parkinson's disease model. J Cell Biol 2011; 192(5): 873-82.
  3. Thomas B, Beal MF. Molecular insights into Parkinson's disease. F1000 Med Rep 2011; 3: 7.
  4. Potashkin JA, Blume SR, Runkle NK. Limitations of animal models of Parkinson's disease. Parkinsons Dis 2010; 2011: 658083.
  5. Ogata A, Tashiro K, Nukuzuma S, Nagashima K, Hall WW. A rat model of Parkinson's disease induced by Japanese encephalitis virus. J Neurovirol 1997; 3(2): 141-7.
  6. Fishman PS, Gass JS, Swoveland PT, Lavi E, Highkin MK, Weiss SR. Infection of the basal ganglia by a murine coronavirus. Science 1985; 229(4716): 877-9.
  7. Takahashi M, Yamada T, Nakajima S, Nakajima K, Yamamoto T, Okada H. The substantia nigra is a major target for neurovirulent influenza A virus. J Exp Med 1995; 181(6): 2161-9.
  8. Bove J, Prou D, Perier C, Przedborski S. Toxin-induced models of Parkinson's disease. NeuroRx 2005; 2(3): 484-94.
  9. Shen WB, McDowell KA, Siebert AA, Clark SM, Dugger NV, Valentino KM, et al. Environmental neurotoxin-induced progressive model of parkinsonism in rats. Ann Neurol 2010; 68(1): 70-80.
  10. Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. Neuron 2003; 39(6): 889-909.
  11. Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT. A highly reproducible rotenone model of Parkinson's disease. Neurobiol Dis 2009; 34(2): 279-90.
  12. Newhouse K, Hsuan SL, Chang SH, Cai B, Wang Y, Xia Z. Rotenone-induced apoptosis is mediated by p38 and JNK MAP kinases in human dopaminergic SH-SY5Y cells. Toxicol Sci 2004; 79(1): 137-46.
  13. Urbach YK, Bode FJ, Nguyen HP, Riess O, von HS. Neurobehavioral tests in rat models of degenerative brain diseases. Methods Mol Biol 2010; 597: 333-56.
  14. Xiong N, Xiong J, Khare G, Chen C, Huang J, Zhao Y, et al. Edaravone guards dopamine neurons in a rotenone model for Parkinson's disease. PLoS One 2011; 6(6): e20677.
  15. Fleming SM, Zhu C, Fernagut PO, Mehta A, DiCarlo CD, Seaman RL, et al. Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone. Exp Neurol 2004; 187(2): 418-29.
  16. Phinney AL, Andringa G, Bol JG, Wolters EC, van Muiswinkel FL, van Dam AM, et al. Enhanced sensitivity of dopaminergic neurons to rotenone-induced toxicity with aging. Parkinsonism Relat Disord 2006; 12(4): 228-38.
  17. Betarbet R, Canet-Aviles RM, Sherer TB, Mastroberardino PG, McLendon C, Kim JH, et al. Intersecting pathways to neurodegeneration in Parkinson's disease: effects of the pesticide rotenone on DJ-1, alpha-synuclein, and the ubiquitin-proteasome system. Neurobiol Dis 2006; 22(2): 404-20.
  18. Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, et al. Mechanism of toxicity in rotenone models of Parkinson's disease. J Neurosci 2003; 23(34): 10756-64.
  19. Iancu R, Mohapel P, Brundin P, Paul G. Behavioral characterization of a unilateral 6-OHDA-lesion model of Parkinson's disease in mice. Behav Brain Res 2005; 162(1): 1-10.