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CC BY-NC-ND 4.0 · Journal of Health and Allied Sciences NU 2021; 11(03): 158-163
DOI: 10.1055/s-0041-1726690
Original Article

Establishing the Rotenone-Induced Parkinson's Disease Animal Model in Wistar Albino Rats

Gangadhara Swamy
1   Department of Anatomy, Subbiah Institute of Medical Sciences and Research Center, Shivamogga, Karnataka, India
,
Rajendra Holla
2   Department of Pharmacology, K.S. Hegde Medical Academy, Mangalore, Karnataka, India
,
Suresh R. Rao
1   Department of Anatomy, Subbiah Institute of Medical Sciences and Research Center, Shivamogga, Karnataka, India
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Abstract

Objective The aim of this study was to establish the safe and effective dose of rotenone-induced Parkinson’s disease (PD) in Wistar albino rat.

Materials and Methods Male Wistar albino rats (n = 6) aged between 9 and 11 weeks, weight 200 to 250 g, were selected for the study. Rats were divided into four groups namely, A, B, C, and D; Group A served as control received only isotonic saline, groups B, C, and D were administered with rotenone 2, 2.5, and 3 mg/kg body weight (BW), respectively, with a specialized vehicle through intraperitoneal (IP) route once daily. During the procedure, they were observed for the development of the PD signs such as stooped posture, postural instability, akinesia, bradykinesia, and muscular rigidity. BW and behavioral pattern were recorded before the rotenone introduction and also after the onset of PD signs in them. They were sacrificed when the PD phenotype became debilitating and followed by neurochemical assay for dopamine and antioxidants; histological assay for TH-neuronal density and Lewy bodies were performed in the substantia nigra pars compacta (SNpc) of midbrain.

Results Group C and D animals were developed with the PD signs by the 9th day and also there was a significant decrease in the BW noticed in them. Additionally, histological studies revealed the decrease in neuronal density and the presence of Lewy bodies in the dopamine neurons of the SNpc. However, it was also noticed that the group D had shown more mortality rate when compared with the Group C.

Conclusion Rotenone with 2.5 mg/kg BW IP was an ideal dose to develop PD signs in Wistar albino rats model that is a highly reproducible and may offer an excellent tool to establish the new neuroprotective treatment strategies.

Keywords

Parkinson’s disease - rotenone - immunohistochemistry - Lewy body and dopamine


Publication History

Article published online:
18 May 2021

© 2021. Nitte (Deemed to be University). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Braak H, Braak E. Pathoanatomy of Parkinson’s disease. J Neurol 2000; 247 (02) II3-II10
    CrossrefPubMedSearch in Google Scholar
  • 2 Parkinson J. An essay on the shaking palsy. 1817. J Neuropsy-chiatry Clin Neurosci 2002; 14 (02) 223-236
    CrossrefPubMedSearch in Google Scholar
  • 3 Chang YP, Yang CJ, Hu KF. et al. Risk factors for pneumonia among patients with Parkinson’s disease: a Taiwan nationwide population-based study. Neuropsychiatr Dis Treat 2016; 12: 1037-1046
    CrossrefPubMedSearch in Google Scholar
  • 4 Guridi J, Lozano AM, Lozano AM. A brief history of pallidotomy. Neurosurgery 1997; 41 (05) 1169-1180
    CrossrefPubMedSearch in Google Scholar
  • 5 Goldman SM. Environmental toxins and Parkinson’s disease. Annu Rev Pharmacol Toxicol 2014; 54: 141-164
    CrossrefPubMedSearch in Google Scholar
  • 6 Marey-Semper I, Gelman M, Lévi-Strauss M. A selective toxicity toward cultured mesencephalic dopaminergic neurons is induced by the synergistic effects of energetic metabolism impairment and NMDA receptor activation. J Neurosci 1995; 15 (09) 5912-5918
    CrossrefPubMedSearch in Google Scholar
  • 7 Pritchett-Corning KR, Chang FT, Festing MF. Breeding and housing laboratory rats and mice in the same room does not affect the growth or reproduction of either species. J Am Assoc Lab Anim Sci 2009; 48 (05) 492-498
    PubMedSearch in Google Scholar
  • 8 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 (02) 279-290
    CrossrefPubMedSearch in Google Scholar
  • 9 Fleming SM, Zhu C, Fernagut PO. et al. Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone. Exp Neurol 2004; 187 (02) 418-429
    CrossrefPubMedSearch in Google Scholar
  • 10 Woodlee MT, Kane JR, Chang J, Cormack LK, Schallert T. Enhanced function in the good forelimb of hemi-Parkinson rats: compensatory adaptation for contralateral postural instability?. Exp Neurol 2008; 211 (02) 511-517
    CrossrefPubMedSearch in Google Scholar
  • 11 Devi PU, Suresh R, Hande MP. Effect of fetal exposure to ultrasound on the behavior of the adult mouse. Radiat Res 1995; 141 (03) 314-317
    CrossrefPubMedSearch in Google Scholar
  • 12 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 (02) 141-147
    CrossrefPubMedSearch in Google Scholar
  • 13 Park JH, Kang YJ, Horak FB. What is wrong with balance in Parkinson’s disease?. J Mov Disord 2015; 8 (03) 109-114
    CrossrefPubMedSearch in Google Scholar
  • 14 Nair-Roberts RG, Chatelain-Badie SD, Benson E, White-Cooper H, Bolam JP, Ungless MA. Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat. Neuroscience 2008; 152 (04) 1024-1031
    CrossrefPubMedSearch in Google Scholar
  • 15 Sun M, Zhang GR, Kong L. et al. Correction of a rat model of Parkinson’s disease by coexpression of tyrosine hydroxylase and aromatic amino acid decarboxylase from a helper virus-free herpes simplex virus type 1 vector. Hum Gene Ther 2003; 14 (05) 415-424
    CrossrefPubMedSearch in Google Scholar
  • 16 Gao C, Wang AY, Han YJ. Microwave antigen retrieval blocks endogenous peroxidase activity in immunohistochemistry. Appl Immunohistochem Mol Morphol 2008; 16 (04) 393-399
    CrossrefPubMedSearch in Google Scholar
  • 17 Wojnicz A, Ortiz JA, Casas AI, Freitas AE, López MG, Ruiz-Nuño A. Simultaneous determination of 8 neurotransmitters and their metabolites using liquid chromatography in tandem mass spectrometry application to the murine Nrf2 model of depression. Clin Chim Acta 2016; 7: 714-720
    Search in Google Scholar
  • 18 Marttila RJ, Lorentz H, Rinne UK. Oxygen toxicity protecting enzymes in Parkinson’s disease. Increase of superoxide dismutase-like activity in the substantia nigra and basal nucleus. J Neurol Sci 1988; 86 (2-3) 321-331
    CrossrefPubMedSearch in Google Scholar
  • 19 Alam M, Schmidt WJ. Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav Brain Res 2002; 136 (01) 317-324
    CrossrefPubMedSearch in Google Scholar
  • 20 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 (02) 279-290
    CrossrefPubMedSearch in Google Scholar
  • 21 Mbiydzenyuy NE, Ninsiima HI, Valladares MB, Pieme CA. Zinc and linoleic acid pre-treatment attenuates biochemical and histological changes in the midbrain of rats with rotenone-induced Parkinsonism. BMC Neurosci 2018; 19 (01) 29
    CrossrefPubMedSearch in Google Scholar
  • 22 Deumens R, Blokland A, Prickaerts J. Modeling Parkinson’s disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 2002; 175 (02) 303-317
    CrossrefPubMedSearch in Google Scholar
  • 23 Betarbet R, Canet-Aviles RM, Sherer TB. 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 (02) 404-420
    CrossrefPubMedSearch in Google Scholar
  • 24 Fearnley JM, Lees AJ. Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 1991; 114 (Pt 5) 2283-2301
    CrossrefPubMedSearch in Google Scholar
  • 25 Jayaraj RL, Beiram R, Azimullah S. et al. Lycopodium attenuates loss of dopaminergic neurons by suppressing oxidative stress and neuroinflammation in a rat model of Parkinson’s disease. Molecules 2019; 24 (11) 2182
    CrossrefPubMedSearch in Google Scholar