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트레드밀 운동이 파킨슨 유도 모델 쥐의 α-synuclein 발현과 미토콘드리아 구조적 역동성에 미치는 영향

The Effect of Treadmill Exercise on α-synuclein and Mitochondrial Dynamic in The Mouse Model of Parkinson’s Disease

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PURPOSE: The purpose of this study was to investigate the effects of treadmill exercise on motor function, α-synuclein (α-syn), neuronal cell survival, mitochondrial dynamic-related proteins, and sirtuin-3 (SIRT-3) in the MPTP-induced mice model of Parkinson’s disease (PD). METHODS: Twenty four mice model of PD were divided into three groups: (1) Sham control (Sham, n=8), (2) MPTP treatment (MPTP, n=8), and (3) MPTP-Exercise (MPTP-E, n=8). MPTP-E mice group were performed to exercise on a treadmill for 8 weeks (12 m/min, 60 min/day, 5 days/week). In addition, we conducted Rota-rod test to evaluate the motor function. And then, substantia nigra (SN) was evaluated to determine whether any changes in the α-syn, neuronal cell survival, SIRT-3, mitochondrial fission, and fusion proteins. RESULTS: Treadmill exercise rescued motor deficits by reducing α-syn expression and alleviating neuronal cell death in the MPTP-induce mice model of PD. In addition, treadmill exercise increased mitochondrial fusion-related protein (Opa1, Mfn1, Mfn2) and decreased mitochondrial fission-related protein (Fis1, Drp1) possibly via activating SIRT-3 expression in the MPTP-induce mice model of PD. CONCLUSIONS: Treadmill exercise improved motor function by inhibiting neurotoxicity and improving mitochondrial dynamic via reducing α-syn expression and activating SIRT-3 expression. These results indicating that improving mitochondrial dysfunction via treadmill exercise may be potent strategy to alleviate the PD pathogenesis.

Abstract

PURPOSE: The purpose of this study was to investigate the effects of treadmill exercise on motor function, α-synuclein (α-syn), neuronal cell survival, mitochondrial dynamic-related proteins, and sirtuin-3 (SIRT-3) in the MPTP-induced mice model of Parkinson’s disease (PD). METHODS: Twenty four mice model of PD were divided into three groups: (1) Sham control (Sham, n=8), (2) MPTP treatment (MPTP, n=8), and (3) MPTP-Exercise (MPTP-E, n=8). MPTP-E mice group were performed to exercise on a treadmill for 8 weeks (12 m/min, 60 min/day, 5 days/week). In addition, we conducted Rota-rod test to evaluate the motor function. And then, substantia nigra (SN) was evaluated to determine whether any changes in the α-syn, neuronal cell survival, SIRT-3, mitochondrial fission, and fusion proteins. RESULTS: Treadmill exercise rescued motor deficits by reducing α-syn expression and alleviating neuronal cell death in the MPTP-induce mice model of PD. In addition, treadmill exercise increased mitochondrial fusion-related protein (Opa1, Mfn1, Mfn2) and decreased mitochondrial fission-related protein (Fis1, Drp1) possibly via activating SIRT-3 expression in the MPTP-induce mice model of PD. CONCLUSIONS: Treadmill exercise improved motor function by inhibiting neurotoxicity and improving mitochondrial dynamic via reducing α-syn expression and activating SIRT-3 expression. These results indicating that improving mitochondrial dysfunction via treadmill exercise may be potent strategy to alleviate the PD pathogenesis.

참고문헌 (44)

  1. Hirsch MA, "The effects of balance training and high-intensity resistance training on persons with idiopathic Parkinson’s disease", Archives of Physical Medicine and Rehabilitation, 84(8), pp.1109~1117 (2003)
  2. Pringsheim T, "The prevalence of Parkinson’s disease: a systematic review and meta-analysis", Movement Disorder, 29(13), pp.1583~1590 (2014)
  3. Schapira AH, "Aetiopathogenesis of Parkinson’s disease", Journal of Neurology, 258(Suppl 2), pp.S307~S310 (2011)
  4. Murphy DD, "Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons", The Journal of Neuroscience, 20(9), pp.3214~3220 (2000)
  5. Fortin DL, "Neural activity controls the synaptic accumulation of alpha-synuclein", The Journal of Neuroscience, 25(47), pp.10913~10921 (2005)
  6. Chu Y, "Alterations in axonal transport motor proteins in sporadic and experimental Parkinson’s disease", Brain, 135(Pt 7), pp.2058~2073 (2012)
  7. Martin LJ, "Mitochondrial permeability transition pore regulates Parkinson’s disease development in mutant α-synuclein transgenic mice", Neurobiology of Aging, 35(5), pp.1132~1152 (2014)
  8. Roberts HL, "Seeking a mechanism for the toxicity of oligomeric α-synuclein", Biomolecules, 5(2), pp.282~305 (2015)
  9. Winner B, "In vivo demonstration that alpha-synuclein oligomers are toxic", Proceeding of National Academy of Science of the United States of America, 108(10), pp.4194~4199 (2011)
  10. Bender A, "TOM40 mediates mitochondrial dysfunction induced by α-synuclein accumulation in Parkinson’s disease", PLoS One, 8(4), pp.e62277~ (2013)
  11. Chen H, "Mitochondrial dynamics--fusion, fission, movement, and mitophagy--in neurodegenerative diseases", Human Molecular Genetics, 18(R2), pp.R169~R176 (2009)
  12. Xie W, "Alpha-synuclein impairs normal dynamics of mitochondria in cell and animal models of Parkinson’s disease", Journal of Neurochemistry, 122(2), pp.404~414 (2012)
  13. Kamp F, "Inhibition of mitochondrial fusion by α-synuclein is rescued by PINK1, Parkin and DJ-1", The EMBO Jorunal, 29(20), pp.3571~3589 (2010)
  14. Gui YX, "Extracellular signal-regulated kinase is involved in alpha-synuclein-induced mitochondrial dynamic disorders by regulating dynamin-like protein 1", Neurobiology of Aging, 33(12), pp.2841~2854 (2012)
  15. Nakamura K, "Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein", The Journal of Biological Chemistry, 286(23), pp.20710~20726 (2011)
  16. Hüttenrauch M, "Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model", Translational Psychiatry, 6(5), pp.e800~ (2016)
  17. Li L, "Moderate exercise prevents neurodegeneration in D-galactose-induced aging mice", Neural Regeneration Research, 11(5), pp.807~815 (2016)
  18. Yan Z, "Exercise training-induced regulation of mitochondrial quality", Exercise and Sport Scienece Reviews, 40(3), pp.159~164 (2012)
  19. Smith BA, "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 Research, 1386, pp.70~80 (2011)
  20. Real CC, "BDNF receptor blockade hinders the beneficial effects of exercise in a rat model of Parkinson’s disease", Neuroscience, 237, pp.118~129 (2013)
  21. Tuon T, "Physical training prevents depressive symptoms and a decrease in brain-derived neurotrophic factor in Parkinson’s disease", Brain Research Bulletin, 108, pp.106~112 (2014)
  22. Tuon T, "Physical training exerts neuroprotective effects in the regulation of neurochemical factors in an animal model of Parkinson’s disease", Neuroscience, 227, pp.305~312 (2012)
  23. Lau YS, "Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson’s disease with moderate neurodegeneration", The Euroupean Journal of Neuroscience, 33(7), pp.1264~1274 (2011)
  24. Mandel S, "Iron and alpha-synuclein in the substantia nigra of MPTP-treated mice: effect of neuroprotective drugs Rapomorphine and green tea polyphenol (-)-epigallocatechin-3-gallate", Journal of Molecular Neuroscience, 24(3), pp.401~416 (2004)
  25. Meredith GE, "Modeling PD pathogenesis in mice: advantages of a chronic MPTP protocol", Parkinsonism & Related Disorders, 14(Suppl 2), pp.S112~S115 (2008)
  26. Kowall NW, "MPTP induces alpha-synuclein aggregation in the substantia nigra of baboons", Neuroreport, 11(1), pp.211~213 (2000)
  27. Chen M, "Tea polyphenols alleviate motor impairments, dopaminergic neuronal injury, and cerebral α-synuclein aggregation in MPTP-intoxicated parkinsonian monkeys", Neuroscience, 286, pp.383~392 (2015)
  28. Li XH, "7, 8-dihydroxyflavone Ameliorates motor deficits via suppressing α-synuclein expression and oxidative stress in the MPTP-induced mouse model of parkinson’s disease", CNS Neuroscience & Therapeutics, 22(7), pp.617~624 (2016)
  29. Liu L, "Protective role of SIRT5 against motor deficit and dopaminergic degeneration in MPTP-induced mice model of Parkinson’s disease", Behavioural Brain Research, 281, pp.215~221 (2015)
  30. Klein C, "Physical exercise counteracts MPTP-induced changes in neural precursor cell proliferation in the hippocampus and restores spatial learning but not memory performance in the water maze", Behavioural Brain Research, 307, pp.227~238 (2016)
  31. Shin MS, "Treadmill exercise facilitates synaptic plasticity on dopaminergic neurons and fibers in the mouse model with Parkinson’s disease", Neuroscience Letters, 621, pp.28~233 (2016)
  32. Fornai F, "Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin-proteasome system and alpha-synuclein", Proceeding of the National Academy of Science of United States of America, 102(9), pp.3413~3418 (2005)
  33. Shioda N, "FABP3protein promotes α-synuclein oligomerization associated with 1-methyl-1,2,3,6-tetrahydropiridine-induced neurotoxicity", The Journal of Biological Chemistry, 289(27), pp.18957~18965 (2014)
  34. Heng Y, "Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTPprobenecid-induced parkinsonism mouse model by targeting α-synuclein abnormalities in the substantia nigra", Toxicology Letters, 243, pp.7~21 (2016)
  35. Requejo-Aguilar R, "Mitochondrial control of cell bioenergetics in Parkinson’s disease", Free Radical Biology & Medicine, (16), pp.S0891~S5849 (2016)
  36. Von Stockum S, "Mitochondrial dynamics and mitophagy in Parkinson’s disease: A fly point of view", Neurobiology of Disease, 90, pp.58~67 (2016)
  37. Westermann B, "Mitochondrial fusion and fission in cell life and death. Nature Reviews", Molecular Cell Biology, 11(12), pp.872~884 (2010)
  38. Chan DC, "Mitochondrial fusion and fission in mammals", Annual Review of Cell and Development Biology, 22, pp.79~99 (2006)
  39. Duan W, "Sirtuins: from metabolic regulation to brain aging", Frontiers in Aging Neuroscience, 5, pp.36~ (2013)
  40. Kincaid B, "Forever young: SIRT3 a shield against mitochondrial meltdown, aging, and neurodegeneration", Frontiers in Aging Neuroscience, 5, pp.48~ (2013)
  41. Morigi M, "Sirtuin 3-dependent mitochondrial dynamic improvements protect against acute kidney injury", The Journal of Clinical Investigation, 125(2), pp.715~726 (2015)
  42. Samant SA, "SIRT3deacetylates and activates OPA1 to regulate mitochondrial dynamics during stress", Molecular and Cell Biology, 34(5), pp.807~819 (2014)
  43. Young JS, "Synchrony between sensory and cognitive networks is associated with subclinical variation in autistic traits", Frontier in Human Neuroscience, 9, pp.146~ (2015)
  44. Vargas-Ortiz K, "Aerobic training increases expression levels of SIRT3 and PGC-1α in skeletal muscle of overweight adolescents without change in caloric intake", Pediatric Exercise Science, 27(2), pp.177~184 (2015)

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