View More View Less
  • 1 Department of Physiology, Saveetha Medical College Hospital, Saveetha Nagar, Thandalam, Chennai, India
  • 2 Department of Research and Development, Saveetha Institute of Medical and Technical Sciences, Chennai, India
  • 3 Department of Chemistry, Siddha Central Research Institute, Arumbakkam, Chennai, India
  • 4 Department of Veterinary Pathology, Madras Veterinary College, Chennai, India
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $752.00

Abstract

Objective

Parkinson's disease (PD) is a progressive neurodegenerative disorder. In order to explore a noninvasive treatment of PD, in the current study the authors evaluated the neuroprotective efficacy of caloric vestibular stimulation (CVS) using the rotenone-induced rat model of PD. The rotenone models of PD are gaining attention due to high reproducibility. It is also considered to be an improved model to exhibit the pathogenesis of PD and test the neuroprotective effect of various therapeutic interventions.

Materials and methods

Rotenone was i.p. injected (3 mg/kg body weight) to male Wistar albino rats for 21 days to induce PD. As PD is chronic and progressive in nature, the efficacy of chronic CVS intervention was evaluated for 30 days after inducing PD in rats. Motor symptoms were evaluated by assessing locomotor activity in actophotometer, whereas movement analysis was done using Ludolph test and motor coordination was evaluated using rotarod apparatus. The neurochemical and neuropathological changes were also observed in the corpus striatum of rats.

Results

Rotenone administration showed decreased locomotor activity, motor coordination and general movement associated with significant (P < 0.05) reduction in dopamine content in the corpus striatum. The immunohistochemical analysis revealed a marked decrease in tyrosine hydroxylase (TH) immunoreactivity in striatal neurons indicating the significant loss of dopaminergic neurons in substantia nigra (SN) following rotenone injection. However, chronic treatment with CVS restored the nerve terminals in the striatum from rotenone damage. CVS treatment improved the dopaminergic system function by restoring dopamine content in the striatum. CVS also improved the motor deformities clearly suggesting the neuroprotective function.

Conclusion

The results of the present study suggested CVS to be a safe and simple neuroprotective measure against neurodegenerative changes in PD and a promising noninvasive technique to overcome the motor symptoms associated with it. The findings could be useful for further investigations and clinical applications of CVS in the treatment of PD.

  • 1.

    Bishnoi M, Chopra K, Kulkarni SK. Involvement of adenosinergic receptor system in an animal model of tardive dyskinesia and associated behavioural, biochemical and neurochemical changes. Eur J Pharmacol 2006; 552: 5566.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    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: 27990.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Grimbergen YA, Munneke M, Bloem BR. Falls in Parkinson's disease. Curr Opin Neurol 2004; 17: 40515.

  • 4.

    Lerman SF, Bronner G, Cohen OS, Elincx-Benizri S, Strauss H, Yahalom G, . Catastrophizing mediates the relationship between non-motor symptoms and quality of life in Parkinson's disease. Disabil Health J 2019; 12: 6738.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Parkinson G. Disease survey steering committee. factors impacting on quality of life in Parkinson’s disease: results from an international survey. Mov Disord 2002; 17: 607.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nature Neurosci 2000; 3: 13016.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Smith TS, Parker JW, Bennett JJ. L-dopa increases nigral production of hydroxyl radicals in vivo: potential L-dopa toxicity? Neuroreport 1994; 5: 100911.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    deSouza RM, Moro E, Lang AE, Schapira AH. Timing of deep brain stimulation in Parkinson disease: a need for reappraisal? Annal Neurol 2013; 73: 56575.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Utz KS, Dimova V, Oppenländer K, Kerkhoff G. Electrified minds: transcranial direct current stimulation (tDCS) and galvanic vestibular stimulation (GVS) as methods of non-invasive brain stimulation in neuropsychology—a review of current data and future implications. Neuropsychologia 2010; 48: 2789810.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Smith PF. Vestibular functions and Parkinson's disease. Front Neurol 2018; 9: 1085.

  • 11.

    Sailesh SK, Archana R, Mukkadan JK. Controlled vestibular stimulation: a physiological method of stress relief. J Clin Diagn Res 2014; 8: BM0102.

    • Search Google Scholar
    • Export Citation
  • 12.

    Wilkinson D, Podlewska A, Banducci SE, Pellat-Higgins T, Slade M, Bodani M, . Caloric vestibular stimulation for the management of motor and non-motor symptoms in Parkinson's disease: intention-to-treat data. Data Brief 2019; 25: 104228.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Wilkinson D, Podlewska A, Banducci SE, Pellat-Higgins T, Slade M, Bodani M, . Caloric vestibular stimulation for the management of motor and non-motor symptoms in Parkinson's disease. Parkinsonism Relat Disord 2019; 65: 2616.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Nishiike S, Takeda N, Kubo T, Nakamura S. Neurons in rostral ventrolateral medulla mediate vestibular inhibition of locus coeruleus in rats. Neuroscience 1997; 77: 21932.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Nishiike S, Takeda N, Uno A, Kubo T, Yamatodani A, Nakamura S. Cholinergic influence on vestibular stimulation-induced locus coeruleus inhibition in rats. Acta oto-laryngologica 2000; 120: 4049.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Ludolph A, He F, Spencer P, Hammerstad J, Sabri M. 3-Nitropropionic acid-exogenous animal neurotoxin and possible human striatal toxin. Can J Neurol Sci 1991; 18: 4928.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Kishore Kumar SN, Deepthy J, Saraswathi U, Thangarajeswari M, Yogesh Kanna S, . Morinda citrifolia mitigates rotenone-induced striatal neuronal loss in male Sprague-Dawley rats by preventing mitochondrial pathway of intrinsic apoptosis. Redox Report 2017; 22: 41829.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Gu M-J, Jeon J-H, Oh MS, Hong S-P. Measuring levels of biogenic amines and their metabolites in rat brain tissue using high-performance liquid chromatography with photodiode array detection. Archives Pharmacal Res 2016; 39: 5965.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Pangestiningsih TW, Wendo WD, Selan YN, Amalo FA, Ndaong NA, Lenda V. Histological features of catecholaminergic neuron in substantia nigra induced by paraquat dichloride (1,1-dimethyl-4,4 bipyridinium) in Wistar rat as a model of Parkinson disease. Indonesian J Biotechnol 2014; 19: 918.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Johnson ME, 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. Neurotoxicology 2015; 46: 10116.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Ren Y, Liu W, Jiang H, Jiang Q, Feng J. Selective vulnerability of dopaminergic neurons to microtubule depolymerization. J Biol Chem 2005; 280: 3410512.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Sanders LH, Greenamyre JT. Oxidative damage to macromolecules in human Parkinson disease and the rotenone model. Free Radical Biol Med 2013; 62: 11120.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Nehru B, Verma R, Khanna P, Sharma SK. Behavioral alterations in rotenone model of Parkinson's disease: attenuation by co-treatment of centrophenoxine. Brain Res 2008; 1201: 1227.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    von Wrangel C, Schwabe K, John N, Krauss JK, Alam M. The rotenone-induced rat model of Parkinson's disease: behavioral and electrophysiological findings. Behav Brain Res 2015; 279: 5261.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Sailesh KS, Archana R. Effect of caloric vestibular stimulation on brain neurotransmitters in an MPTP-induced mouse model of Parkinson's disease. Int J Res Pharm Sci 2019; 10: 404.

    • Search Google Scholar
    • Export Citation
  • 26.

    Rancz EA, Moya J, Drawitsch F, Brichta AM, Canals S, Margrie TW. Widespread vestibular activation of the rodent cortex. J Neurosci 2015; 35: 592634.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Stiles L, Reynolds JN, Napper R, Zheng Y, Smith PF. Single neuron activity and c‐Fos expression in the rat striatum following electrical stimulation of the peripheral vestibular system. Physiological Report 2018; 6: e13791.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Alam M, Schmidt W. Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav Brain Res 2002; 136: 31724.

  • 29.

    Richter A, Ebert U, Nobrega J, Vallbacka J, Fedrowitz M, Löscher W. Immunohistochemical and neurochemical studies on nigral and striatal functions in the circling (ci) rat, a genetic animal model with spontaneous rotational behavior. Neuroscience 1999; 89: 46171.

    • Crossref
    • Search Google Scholar
    • Export Citation

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Aug 2020 0 0 0
Sep 2020 0 0 0
Oct 2020 61 1 1
Nov 2020 182 8 6
Dec 2020 105 1 2
Jan 2021 66 0 0
Feb 2021 0 0 0