Parkinsonian Lesion in Rat Induced by Rotenone and its Possible Mechanism

Abstract

Abstract: Objective To estimate the behavioral defects, pathological abnormalities, and biochemical changes after rotenone injection in rats, and study the associated mechanisms of Parkinson's disease (PD). Methods To induce the Parkinsonian lesions, rats got a stereotaxic injection of rotenone into the substantia nigra pars compacta. Behavioral performances were estimated by rotarod test and apomorphine induced rotation; pathological abnormalities were examined by immunohistochemistry; biochemical changes were detected by western blot. Results Unilateral stereotaxic infusion of rotenone led to behavioral defects of rats and resulted in rotations after rats treated by apomorphine. The pathological and biochemical results showed that rotenone had caused loss of dopaminergic neurons, phosphorylation of α-synuclein, activation of microglia, and increased protein content of tumor necrosis factor (TNF-α) and cyclooxygenase-2 (COX-2). Conclusion Rotenone may initiate and promote the neurodegeneration of PD by destroying dopaminergic neurons, inducing α-synuclein phosphorylation, activating microglia, and increasing the protein content of TNF-α and COX-2.

Key words: Parkinson's disease, rotenone, stereotaxic infusion, α-synuclein, neuroinflammation

CLC Number:

R965

ZHANG Qiu-shuang, CHEN Ying, CHEN Nai-hong, YUAN Yu-he. Parkinsonian Lesion in Rat Induced by Rotenone and its Possible Mechanism[J]. Chinese Journal of Pharmacovigilance, 2017, 14(9): 513-517.

References

[1] Connolly B S, Lang A E. Pharmacological treatment of Parkinson disease: a review[J]. Jama, 2014, 311(16):1670.
[2] Johnson M E, Bobrovskaya L. An update on the rotenone models of Parkinson's disease: Their ability to reproduce the features of clinical disease and model gene-environment interactions[J]. Neurotoxicology, 2015, 46:101.
[3] Zhang S, Shao S Y, Song X Y, et al. Protective effects of Forsythia suspense, extract with antioxidant and anti-inflammatory properties in a model of rotenone induced neurotoxicity[J]. Neurotoxicology, 2015, 52:72-83.
[4] Wang Y, Shi M, Chung K A, et al. Phosphorylated alpha-synuclein in Parkinson's disease[J]. Science Translational Medicine, 2012, 4(6): 1-27.
[5] Sacino A N, Brooks M, McGarvey N H, et al. Induction of CNS alpha-synuclein pathology by fibrillar and non-amyloidogenic recombinant alpha-synuclein[J]. Acta neuropathologica communications 2013, 1: 38.
[6] Tenreiro S, Eckermann K, Outeiro T F. Protein phosphorylation in neurodegeneration: friend or foe?[J]. Front Mol Neurosci, 2014, 7:42.
[7] Ouchi Y, Yoshikawa E, Sekine Y, et al. Microglial activation and dopamine terminal loss in early Parkinson's disease[J]. Annals of Neurology, 2005, 57(2):168.
[8] Gerhard A, Pavese N, Hotton G, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease.[J]. Neurobiology of Disease, 2006, 21(2):404-412.
[9] Soulet D, Rivest S. Microglia[J]. Current Biology Cb, 2008, 18(12):R506.
[10] Zhang Q S, Heng Y, Yuan Y H, et al. Pathological-synuclein exacerbates the progression of Parkinson's disease through microglial activation[J]. Toxicology Letters, 2016, 265:30-37.
[11] Blumdegen D, Müller T, Kuhn W, et al. Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients.[J]. Neuroscience Letters, 1995, 202(1-2):17-20.
[12] Mogi M, Harada M, Riederer P, et al. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients[J]. Neuroscience Letters, 1994, 165(1-2):208.
[13] Gagne J J, Power M C. Anti-inflammatory drugs and risk of Parkinson disease: A meta-analysis[J]. Neurology, 2010, 74(12):995.
[14] Manthripragada A D, Schernhammer A E S, Qiu A C D J, et al. Non-steroidal anti-inflammatory drug use and the risk of Parkinson's disease.[J]. Neuroepidemiology, 2011, 36(3):155-161.
[15] Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases[J]. J Neuropathol Exp Neurol, 2004, 63(9):901.
[16] Knott C, Stern G, Wilkin G P. Inflammatory Regulators in Parkinson's Disease: iNOS, Lipocortin-1, and Cyclooxygenases-1 and -2[J]. Molecular & Cellular Neuroscience, 2000, 16(6):724.
[17] Sindhu K M, Banerjee R, Senthilkumar K S, et al. Rats with unilateral median forebrain bundle, but not striatal or nigral, lesions by the neurotoxins MPP+ or rotenone display differential sensitivity to amphetamine and apomorphine[J]. Pharmacology Biochemistry & Behavior, 2006, 84(2):321-329.
[18] Sindhu K M, Saravanan K S, Mohanakumar K P. Behavioral differences in a rotenone-induced hemiparkinsonian rat model developed following intranigral or median forebrain bundle infusion[J]. Brain Research, 2005, 1051(1-2):25-34.