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http://dx.doi.org/10.12925/jkocs.2020.37.4.744

The effect of endurance exercise and MitoQ intake on pathological characteristics in MPTP-induced animal model of Parkinson's disease  

Kim, Dong-Cheol (Exercise biochemistry Laboratory, Korea National Sport University)
Um, Hyun Seob (Department of Sports Medicine, Konyang University)
Oh, Eun-Tak (Department of Sports Science & Rehabilitation, Woosong University)
Cho, Joon-Yong (Department of Health and Exercise Science, Korea National Sport University)
Jang, Yongchul (Exercise biochemistry Laboratory, Korea National Sport University)
Publication Information
Journal of the Korean Applied Science and Technology / v.37, no.4, 2020 , pp. 744-754 More about this Journal
Abstract
We investigated the whether endurance exercise and MitoQ intake mediated neuroprotection are associated with mitochondrial function in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine(MPTP) -induced mice model of Parkinson's disease. C57BL/6 male mice were randomly assigned to five groups: Normal Conrol(NC, n=10), MPTP Control(MC, n=10), MPTP +MitoQ(MQ, n=10), MPTP + Exercise(ME, n=10) and MPTP + MitoQ + Exercise(MQE, n=10). Exercise intervention groups performed the treadmill exercise for 5days/week for 5 weeks with gradual increase of intensity. MitoQ intake groups consumed the MitoQ at a concentration of 250μmol by dissolving with water during experiment period. Our data demonstrated that ME and MQE group restored MPTP-induced motor dysfunction. In addition, treatment groups(MQ, ME and MQE) increased tyrosine hydroxylase levels, and suppressed the accumulation of α-synuclein levels. Futhermore, treatment groups modulated the mitochondrial function such as upregulated mitochondrial biogenesis, increased antioxidant enzyme, enhanced a anti-apoptotic protein(e.g., BCL2), and reduced a pro-apoptotic protein(e.g., BAX). Taken together, these results suggested that endurance exercise and MitoQ intake-mediated increase in mitochondrial function contributes to improvement of aggravated dopaminergic neuronal, resulting in attenuation of motor function of Parkinson's disease.
Keywords
Parkinson's disease; endurance exercise; MitoQ; ${\alpha}$-synuclein; mitochondria;
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1 M.R. Cookson, "Parkinsonism due to mutations in PINK1, parkin, and DJ-1 and oxidative stress and mitochondrial pathways", Cold Spring Harbor Perspectives in Medicine, Vol.2, No.9 a009415, (2012).   DOI
2 J.H. Park,J.D. Burgess, A.H. Faroqi, N.N. DeMeo, F.C. Fiesel, W. Springer, M. Delenclos, P.J. McLean, "Alpha-synucleininduced mitochondrial dysfunction is mediated via a sirtuin 3-dependent pathway", Molecular Neurodegeneration, Vol.15, No.1 s13024-019-0349, (2020).
3 J.H. Koo, J.Y.Cho, "Treadmill Exercise Attenuates $\alpha$-Synuclein Levels by Promoting Mitochondrial Function and Autophagy Possibly via SIRT1 in the Chronic MPTP/P-Induced Mouse Model of Parkinson's Disease", Neurotoxicity Research, Vol.32, No.3 pp. 473-486, (2017).   DOI
4 Y. Xi, D.Feng, K. Tao, R. Wang, Y. Shi, H. Qin, M.P. Murphy, Q. Yang, G. Zhao, "MitoQ protects dopaminergic neurons in a 6-OHDA induced PD model by enhancing Mfn2-dependent mitochondrial fusion via activation of PGC-$1{\alpha}$", Biochimica et Biophysica Acta-Molecular Basis of Disease, Vol.2864, No.9 pp. 2859-2870, (2018).
5 J.A. Obeso, M.C. Rodriguez-Oroz, C.G. Goetz, C. Marin, J.H. Kordower, M.Rodriguez, E.C. Hirsch, M. Farrer, A.H. Schapira, G. Halliday, "Missing piecesin the Parkinson's disease puzzle", Nature Medicine, Vol.16, No.6 pp. 653-661, (2010).   DOI
6 L.V. Kalia,A.E. Lang, "Parkinson's disease", The Lancet, Vol.386, No.9996 pp. 896-912, (2015).   DOI
7 C. Ciron, L.Zheng, W. Bobela, G.W. Knott, T.C. Leone, D.P. Kelly, B.L. Schneider, "PGC-$1{\alpha}$ activity in nigral dopamine neurons determines vulnerability to $\alpha$-synuclein", Acta Neuropathologica Communications, Vol.3, No.16 s40478-015-0200-8, (2015).
8 Y.C. Jang ,D.J. Hwang, J.H. Koo, H.S. Um, N.H. Lee, D.C. Yeom, Y. Lee, J.Y. Cho, "Association of exercise-induced autophagy upregulation and apoptosiss uppression with neuroprotection against pharmacologically induced Parkinson's disease", J Exerc Nutrition Biochem, Vol.22, No.1 pp. 1-8, (2018).   DOI
9 A.B. Singleton,M. Farrer, J. Johnson, A. Singleton, S. Hague, J. Kachergus, M. Hulihan, T.Peuralinna, A. Dutra, R. Nussbaum, S. Lincoln, A. Crawley, M. Hanson, D.Maraganore, C. Adler, M.R. Cookson, M. Muenter, M. Baptista, D. Miller, J.Blancato, J. Hardy, K. Gwinn-Hardy, "alpha-Synuclein locus triplication causesParkinson's disease", Science, Vol.302, No5646 pp. 841, (2003).   DOI
10 S.W. Tait, D.R.Green, "Mitochondrial regulation of cell death", Cold Spring Harbor Perspectives in Biology, Vol.15, No.9 a008706, (2013).
11 G.M. Petzinger,B.E. Fisher, S. McEwen, J.A. Beeler, J.P. Walsh, M.W. Jakowec, "Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease", The Lancet Neurology, Vol.12, No7 pp. 716-726, (2013).   DOI
12 J.H. Koo, Y.C.Jang, D.J. Hwang, H.S. Um, N.H. Lee, J.H. Jung, J.Y. Cho, "Treadmill exercise produces neuroprotective effects in a murine model of Parkinson's disease by regulating the TLR2/MyD88/NF-${\kappa}B$ signaling pathway", Neuroscience, Vol.356, pp. 102-113, (2017).   DOI
13 Y. Jang, J.H. Koo, I. Kwon, E.B. Kang, H.S. Um, H. Soya, Y. Lee, J.Y. Cho, "Neuroprotective effects of endurance exercise against neuroinflammation in MPTP-induced Parkinson's disease mice", Brain Research, Vol.1655, pp. 186-193, (2017).   DOI
14 Y. Jang, I.Kwon, W. Song, L.M. Cosio-Lima, S. Taylor, Y. Lee, "Modulation of mitochondrial phenotypes by endurance exercise contributes to neuroprotection against a MPTP-induced animal model of PD", Life Science, Vol.209, pp. 455-465, (2018).   DOI
15 A.O. Oyewole, M.A. Birch-Machin, "Mitochondria-targeted antioxidants", The FASEB Journal, Vol.29, No.12 pp. 4766-4771, (2015).   DOI
16 Y.S. Lau, G. Patki, K. Das-Panja, W.D. Le, S.O. Ahmad, "Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson's disease with moderate neurodegeneration", European Journal of Neuroscience, Vol.33, No.7 pp. 1264-1274, (2011).   DOI
17 M.J. McManus, M.P. Murphy, J.L. Franklin, "The mitochondria-targeted antioxidant MitoQprevents loss of spatial memory retention and early neuropathology in atransgenic mouse model of Alzheimer's disease", Journal of Neuroscience, Vol.31, No.44 pp. 15703-15715, (2011).   DOI
18 H. Jin, A. Kanthasamy, A. Ghosh, V. Anantharam, B. Kalyanaraman, A.G. Kanthasamy, "Mitochondria-targeted antioxidants for treatment of Parkinson's disease:preclinical and clinical outcomes", Biochimica et Biophysica Acta, Vol.1842, No.8 pp. 1282-1294, (2014).   DOI
19 B.J. Snow,F.L. Rolfe, M.M. Lockhart, C.M. Frampton, J.D. O'Sullivan, V. Fung, R.A. Smith,M.P. Murphy, K.M. Taylor, "A double-blind, placebo-controlled study to assessthe mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease", Movement Disorders, Vol.25, No.11 pp. 1670-1674, (2014).   DOI
20 S.Rodriguez-Cuenca, H.M. Cocheme, A. Logan, I. Abakumova, T.A. Prime, C. Rose, A.Vidal-Puig, A.C. Smith, D.C. Rubinsztein, I.M. Fearnley, B.A. Jones, S. Pope,S.J. Heales, B.Y. Lam, S.G. Neogi, I. McFarlane, A.M. James, R.A. Smith, M.P.Murphy, "Consequences of long-term oral administration of the mitochondriatargeted antioxidant MitoQ to wild-type mice", Free Radical Biology & Medicine, Vol.48, No.1 pp. 161-72, (2010).   DOI
21 M.M Bradford, "A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding", Analytical Biochemistry, Vol.72, No.1-2 pp. 248-254, (1976).   DOI
22 G.E. Meredith,D.J. Rademacher, "MPTP mouse models of Parkinson's disease: an update", Journal of Parkinson's Disease, Vol.1, No.1 pp. 19-33, (2011).   DOI
23 A. Ghosh, K.Chandran, S.V. Kalivendi, J. Joseph, W.E. Antholine, C.J. Hillard, A.Kanthasamy, A. Kanthasamy, B. Kalyanaraman, Neuroprotection by amitochondria-targeted drug in a Parkinson's disease model, Free Radical Biology & Medicine, Vol.49, No.11 pp. 1674-1684, (2010).   DOI
24 G.M.Petzinger, J.P. Walsh, G. Akopian, E. Hogg, A. Abernathy, P. Arevalo, P.Turnquist, M. Vuckovic, B.E. Fisher, D.M. Togasaki, M.W. Jakowec, "Effects of treadmill exercise on dopaminergic transmission in the1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury", Journal of Neuroscience, Vol.27, No.20 pp. 5291- 5300, (2007).   DOI
25 H.F. Shu, T.Yang, S.X. Yu, H.D. Huang, L.L. Jiang, J.W. Gu, Y.Q. Kuang, "Aerobic exercisefor Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials", PLoS One, Vol.9, No.7 pp. e100503, (2014).   DOI
26 H.S. Cho, M.S.Shin, W. Song, T.W. Jun, B.V. Lim, Y.P. Kim, C.J. Kim, "Treadmill exercise alleviates short-term memory impairment in 6-hydroxydopamineinduced Parkinson's rats", Journal of Exercise Rehabilitation, Vol.9, No.3 pp. 354-364, (2013).   DOI
27 L. Xu, J. Pu, "Alpha-Synuclein in Parkinson's Disease: From Pathogenetic Dysfunction to Potential Clinical Application", Parkinson's Disease, Vol.2016, 1720621, (2016).
28 W. Zhou, J.C.Barkow, C.R. Freed, "Running wheel exercise reduces $\alpha$ -synuclein aggregation and improves motor and cognitive function in a transgenic mouse model of Parkinson's disease", PLoS One, Vol.12, No.12 e0190160, (2017).   DOI
29 L. Yang, N.Y.Calingasan, E.J. Wille, K. Cormier, K. Smith, R.J. Ferrante, M.F. Beal, "Combination therapy with coenzyme Q10 and creatine produces additiveneuroprotective effects in models of Parkinson's and Huntington's diseases", Journal of Neurochemistry, Vol.105, No.5 pp. 1427-1439, (2009).