Neuroprotective effects of endurance training in 6-hydroxydopamine rat model of Parkinson’s disease

authors:

avatar Zeinab Rezaee , avatar mohammad marandi , avatar Hojatallah Alaei , * , avatar Fahimeh Esfarjani

Koomesh: Vol.22, issue 3; 556-562
published online: August 01, 2020
article type: Research Article
received: January 01, 2019
accepted: June 01, 2019

how to cite: Rezaee Z, marandi M, Alaei H, Esfarjani F. Neuroprotective effects of endurance training in 6-hydroxydopamine rat model of Parkinson’s disease. koomesh. 2020;22(3):e153214. 

Abstract

Introduction: Parkinson’s disease (PD) is characterized by progressive dopamine depletion in the striatum, and leads to mitochondrial and motor disorders. The present study investigated the effect of moderate endurance training on motor disorder and mRNA expression of PPAR-γ, PGC-1α and BDNF in 6-hydroxydopamine (6-OHDA) rat model of PD Materials and Methods: Thirty two male Wistar rats were divided into 4 eqaul groups: 1. Vehicle (Sham), 2. Vehicle + endurance training, 3. 6-OHDA and 4. 6-OHDA + endurance training. The PD model obtained by unilateral injection of 6-OHDA (8µg/2µl) into the medial forebrain bundle, and the sham group recevied vehicle alone. Two weeks after the surgery, endurance training groups ran on a treadmill 30 min per day for 30 days. Six weeks after the surgery, the rat’s rotations due to apomorphine injection and hippocampal mRNA expression of PPAR-γ, PGC-1α and BDNF were analyzed using Real Time-PCR. Results: 6-OHDA lesioned rats showed increased rotations (P≤0.001), decreased expression of PPAR-γ and BDNF mRNA and compensatory increased in PGC-1α mRNA. Edurance training improved both behavioural and molecular changes. Conclusion: It seems that endurance training can reduce motor disorder and defects in expression of the mitochondrial factors in Parkinson’s disease.

References

  • 1.

    Hosseini M, Rajaei Z, Alaei H. Effects of crocin on rotational behavior, lipid peroxidation and nitrite levels in Rats brain striatum in an experimental model of Parkinson's disease. J Isfahan Med School 2015; 33: 780-791 (Persian).

  • 2.

    Salgado S, Williams N, Kotian R, Salgado M. An evidence-based exercise regimen for patients with mild to moderate Parkinsons disease. Brain Sci 2013; 3: 87-100.

  • 3.

    Siegel GJ, Chauhan NB. Neurotrophic factors in Alzheimer's and Parkinson's disease brain. Brain Res Rev 2000; 33: 199-227.

  • 4.

    Fredriksson A, Stigsdotter IM, Hurtig A, Ewalds-Kvist B, Archer T. Running wheel activity restores MPTP-induced functional deficits. J Neural Transm 2011; 118: 407-420.

  • 5.

    Murray DK, Sacheli MA, Eng JJ, Stoessl AJ. The effects of exerciseon cognition in Parkinsons disease: a systematic review. Transl Neurodegener 2014; 3: 5.

  • 6.

    Aguiar Jr AS, Duzzioni M, Remor AP, Tristo FS, Matheus FC, Raisman-Vozari R, et al. Moderate-intensity physical exercise protects against experimental 6-Hydroxydopamine-induced hemiparkinsonism through Nrf2-antioxidant response element pathway. Neurochem Res 2016; 41: 1-9.

  • 7.

    Cohen AD. Role of Exercise and GDNF in an Animal Model of Parkinson's Disease: Implications for Neuroprotection: University of Pittsburgh; 2006.

  • 8.

    Tuon T, Valvassori SS, Dal Pont GC, Paganini CS, Pozzi BG, Luciano TF, et al. Physical training prevents depressive symptoms and a decrease in brain-derived neurotrophic factor in Parkinson's disease. Brain Res Bull 2014; 108: 106-112.

  • 9.

    Aguiar AS, Castro AA, Moreira EL, Glaser V, Santos AR, Tasca CI, et al. Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats: involvement of hippocampal plasticity via AKT, CREB and BDNF signaling. Mech Ageing Dev 2011; 132: 560-567.

  • 10.

    Aguiar CCT, Almeida AB, Arajo PV, Abreu RN, Chaves EM, Vale OC, et al. Oxidative Stress and Epilepsy: Literature Review. Oxidative Med Cell Longevity 2012; 2012.

  • 11.

    Carta AR, Pisanu A, Carboni E. Do PPAR-Gamma Agonists Have a Future in Parkinson's Disease Therapy? Parkinson's Dis 2011; 2011: 689181.

  • 12.

    Martinez AA, Morgese MG, Pisanu A, Macheda T, Paquette MA, Seillier A, et al. Activation of ppar gamma receptors reduces levodopa-induced dyskinesias in 6-Ohda-Lesioned rats. Neurobiol Dis 2015; 74: 295-304.

  • 13.

    Psilander N. The effect of different exercise regimens on mitochondrial biogenesis and performance. 2014.

  • 14.

    Corona J, Duchen M. PPAR and PGC-1 as Therapeutic Targets in Parkinsons. Neurochem Res 2016; 1-9.

  • 15.

    Mooren F. Molecular and cellular exercise physiology. Human Kinetics; 2005.

  • 16.

    McGough E, Kirk-Sanchez N. Exercise interventions targeting neuroplasticity and neuroprotection in adults with neurodegenerative diseases. Neurodegener Dis 2012.

  • 17.

    Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Haidar EA, Stringer T, et al. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action ofthe ketone body -hydroxybutyrate. Elife 2016; 5: e15092.

  • 18.

    Poulton NP, Muir GD. Treadmill training ameliorates dopamine loss but not behavioral deficits in hemi-Parkinsonian rats. Exper Neurol 2005; 193: 181-197.

  • 19.

    Smith BA, Goldberg NR, Meshul CK. Effects of treadmill exercise on behavioral recovery and neural changes in the substantia nigra and striatum of the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-lesioned mouse. Brain Res 2011; 1386: 70-80.

  • 20.

    LaHue SC, Comella CL, TannerCM. The best medicine? The influence of physical activity and inactivity on Parkinson's disease. Mov Disorder 2016; 31: 1444-1454.

  • 21.

    Costa ROd, Gadelha-Filho CVJ, Costa AEMd, Feitosa ML, jo DPd, Lucena JDd, et al. The Treadmill exercise protectsagainst dopaminergic neuron loss and brain oxidative stress in parkinsonian rats. Oxid Med Cell Longev 2017; 2017: 10.

  • 22.

    Tuon T, Souza PS, Santos MF, Pereira FT, Pedroso GS, Luciano TF, et al. Physical training regulates mitochondrial parameters and neuroinflammatory mechanisms in an experimental model of Parkinsons disease. Oxid Med Cell Longev 2015; 2015: 261809.

  • 23.

    Chen W, Qiao D, Liu X, Shi K. Treadmill exercise improves motor dysfunction and hyperactivity of the corticostriatal glutamatergic pathway in rats with 6-OHDA-Induced Parkinson’s Disease. Neural Plast 2017; 2017: 11.

  • 24.

    Sheibani V, Rafie F, Shahbazi M, Naghdi N, Sheikh M. Comparison of voluntary and forced exercise effects on motor behavior in 6-hydroxydopamine-lesion rat model of Parkinsons disease. Sport Sci Health 2017; 13: 203-211.

  • 25.

    Cho HS, Shin MS, Song W, Jun TW, Lim BV, Kim YP, et al. Treadmill exercise alleviates short-term memory impairment in 6-hydroxydopamine-induced Parkinsons rats. J Exerc Rehabil 2013; 9: 354.

  • 26.

    Yoon MC, Shin MS, Kim TS, Kim BK, Ko IG, Sung YH, et al. Treadmill exercise suppresses nigrostriatal dopaminergic neuronal loss in 6-hydroxydopamine-induced Parkinson's rats. Neurosci Lett 2007; 423: 12-17.

  • 27.

    Real CC, Garcia PC, Britto LRG. Treadmill exercise prevents increase of neuroinflammation markers involved in the dopaminergic damage of the 6-OHDA Parkinsons disease model. J Mol Neurosci 2017; 63: 36-49.

  • 28.

    Fujita KA, Ostaszewski M, Matsuoka Y, Ghosh S, Glaab E, Trefois C, et al. Integrating pathways of Parkinson's disease in a molecular interaction map. Mol Neurobiol 2014; 49: 88-102.

  • 29.

    Steiner JL, Murphy EA, McClellan JL, Carmichael MD, Davis JM. Exercise training increases mitochondrial biogenesis in the brain. J Appl Physiol 2011; 111: 1066-1071.

  • 30.

    Tuon T, Valvassori SS, Lopes-Borges J, Luciano T, Trom CB, Silva LA, et al. Physical training exerts neuroprotective effects in the regulation of neurochemical factors in an animal model of Parkinsons disease. Neuroscience 2012; 227: 305-312.

  • 31.

    Landers MR, Kinney JW, Allen DN, van Breukelen F. A comparison of voluntary and forced exercise in protecting against behavioral asymmetry in a juvenile hemiparkinsonian rat model. Behav Brain Res 2013; 248: 121-128.

  • 32.

    Patki G, Lau Y-S. Impact of exercise on mitochondrial transcription factor expression and damage in the striatum of a chronic mouse model of Parkinson's disease. Neurosci lett 2011; 505: 268-272.

  • 33.

    Razgado-Hernandez LF, Espadas-Alvarez AJ, Reyna-Velazquez P, Sierra-Sanchez A, Anaya-Martinez V, Jimenez-Estrada I, et al. The transfection of BDNF to dopamine neurons potentiates theeffect of dopamine D3 receptor agonist recovering the striatal innervation, dendritic spines and motor behavior in an aged rat model of Parkinsons disease. PloS One 2015; 10: e0117391.

  • 34.

    Mabandla M, Kellaway L, Gibson ASC, Russell VA. Voluntary running provides neuroprotection in rats after 6-hydroxydopamine injection into the medial forebrain bundle. Metab Brain Dis 2004; 19: 43-50.

  • 35.

    Richter EA, Ruderman NB. AMPK and the biochemistry of exercise: implications for human health and disease. Biochem J 2009; 418: 261-275.

  • 36.

    Garcia PC, Real CC, Britto LR. The impact of short and long-term exercise on the expression of Arc and AMPARs during evolution of the 6-Hydroxy-dopamine animal model of Parkinsons disease. J Mol Neurosci 2017; 61: 542-552.

  • 37.

    Rezaee Z, Marandi S-M, Ghaedi K, Esfarjani F. Molecular mechanisms of neurotrophins actions on diseases of nervous system. Genet Third Millennium 2015; 12: 3778-3793 (Persian).

  • 38.

    Dunnett SB. Chapter V Motor function(s) of the nigrostriatal dopamine system: Studies of lesions and behavior.

  • 39.

    Choe M, Koo BS, An GJ, Jeon S. Effects of treadmill exercise on the recovery of dopaminergic neuronloss and muscle atrophy in the 6-ohda lesioned parkinson's disease rat model. Korean J Physiol Pharmacol 2012; 16: 305-312.

  • 40.

    Zigmond MJ, Cameron JL, Leak RK, Mirnics K, Russell VA, Smeyne RJ, et al. Triggering endogenous neuroprotective processes through exercise in models of dopamine deficiency. Parkinsonism Relat Disord 2009; 15: 42-45.

  • 41.

    Chong ZZ, Shang YC, Wang S, Maiese K. SIRT1: new avenues of discovery for disorders of oxidative stress. Expert Opin Ther Targets 2012; 16: 167-178.

  • 42.

    Petzinger GM, Walsh JP, Akopian G, Hogg E, Abernathy A, Arevalo P, et al. Effects of treadmill exercise on dopaminergic transmission in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-lesioned mouse model of basal ganglia injury. J Neurosci 2007; 27: 5291-5300.

  • 43.

    Hou L, Chen W, Liu X, Qiao D, Zhou FM. Exercise-induced neuroprotection of the nigrostriatal dopamine system in Parkinson's disease. Front Aging Neurosci 2017; 9: 358.

  • 44.

    Merrill Russen Landers RL, Frank van Breukelen. Exercise-induced neuroprotection in a hemiparkinsonian 6-hydroxydopamine rat model: University of Nevada, Las Vegas; 2015.