تاثیر تمرین تناوبی شدید و مکمل‌سازی استیل ال-کارنتین بر تیوردوکسین و آلفاسینوکلئین بافت مغز موش‌های نر مدل پارکینسونی

نوع مقاله : مقاله پژوهشی Released under (CC BY-NC 4.0) license I Open Access I

نویسندگان

1 دانشجوی دکتری فیزیولوژی ورزشی، گروه تربیت بدنی و علوم ورزشی، دانشکده علوم انسانی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.

2 دانشیار گروه تربیت بدنی و علوم ورزشی، دانشکده علوم انسانی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز

3 استادیار گروه علوم پایه، دانشکده دامپزشکی، علوم پزشکی تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.

4 استادیار گروه فیزیولوژی ورزشی، گروه تربیت‌بدنی و علوم ورزشی، دانشکده علوم اجتماعی، دانشگاه بین المللی امام خمینی(ره) ، قزوین، ایران

5 استاد گروه پاتوبیولوژی، دانشکده دامپزشکی، علوم پزشکی تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.

چکیده

هدف: بیماری پارکینسون یک‌ بیماری تخریب‌کننده‌عصبی است که‌با از‌بین‌رفتن سلول‌های عصبی دوپامینرژیک در‌ناحیه جسم‌سیاه مغز مشخص‌می‌شود. آلفا‌سینوکلئین پروتئینی است که با‌تشکیل پلاک‌هایی به‌نام لویی‌بادی در بیماری پارکینسون، به‌عنوان عامل‌اصلی آسیب‌های سلولی بافت‌مغز محسوب می‌شود. هدف‌از اجرای پژوهش‌حاضر، تعیین اثر یک دوره تمرین تناوبی‌شدید و مصرف مکمل استیل-ال-کارنتین (ALC) بر‌سطوح پروتئین آلفا‌سینوکلئین و تیوردوکسین (TRX) مغز موش‌های پارکینسونی ناشی‌از 6-هیدروکسی‌دوپامین بود. روش پژوهش: جامعه آماری تحقیق حاضر شامل 36 سر‌رت نر نژاد‌ویستار بودند که بطور‌تصادفی در 6‌ گروه مساوی: گروه‌کنترل سالم، گروه شم‌جراحی، گروه‌کنترل پارکینسون، گروه تمرین پارکینسون، گروه مکمل پارکینسون، گروه تمرین و مکمل پارکینسون، تقسیم شدند. این پژوهش تجربی، در‌مدت 12 هفته تمرین اجرا گردید و گروه‌های دریافت‌کننده دارو، مکمل ALC را یک‌بار در‌روز به‌مدت 12 هفته با دوز mg/kg 100 بصورت گاواژ دریافت کردند. تست‌های رفتاری بمنظور تایید ایجاد مدل پارکینسونی اجرا گردید. نمونه‌های بافتی 48 ساعت پس از آخرین برنامه‌ی تمرین، تهیه شد. یافته‌ها: یافته‌ها نشان دادند پس‌از 12 هفته تمرین HIIT و مصرف ALC، تفاوت معنی‌داری در مقادیر TRX (001/0=P) و‌آلفاسینوکلئین (001/0=P) بین گروه‌های مطالعه وجود داشت. نتایج آزمون‌تعقیبی نشان‌داد که مقادیر TRX و آلفاسینوکلئین در گروه تمرین+مکمل به‌ترتیب بیشترین افزایش (001/0=P) و کاهش (002/0=P) را نسبت به گروه کنترل پارکینسون داشت. تفاوت معنی‌داری در مقادیر آلفاسینوکلئین در گروه‌های تمرین (114/0=p) و مکمل (325/0=p) نسبت به گروه کنترل پارکینسون وجود نداشت. نتیجه‌گیری: تمرین تناوبی شدید همراه‌با مصرف مکمل ALC از‌طریق تعدیل برخی مسیرهای تنظیم‌اکسایشی از‌جمله افزایش آنزیم آنتی‌اکسیدانی TRX و کاهش تجمع آلفاسینوکلئین بافت‌مغز ممکن‌است در بهبود آسیب‌های سلولی و عملکرد بیماران پارکینسونی موثر باشد.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

Effect of High_Intensity Interval Training and Acetyl_L_Carnitine supplementation on Thioredoxin and alpha-synuclein in the brain tissue of male rat model of parkinson,s disease

نویسندگان [English]

  • yousef ghaffari 1
  • Farzad Zehsaz 2
  • Mir Alireza Nourazar 3
  • hasn porrazi 4
  • Daryoush Mohajeri 5
1 Exercise Physiology Ph.D. student, Physical Education & Sport Sciences Department, Faculty of Humanities, Tabriz Branch, Islamic Azad University, Tabriz, Iran
2 Associate Professor, Department of Physical Education & Sport Sciences, Faculty of Humanities, Tabriz Branch, Islamic Azad University, Tabriz
3 Assistant Professor, Department of Basic Sciences, Faculty of Veterinary Medicine, Tabriz Medical Sciences, Islamic Azad University, Tabriz, Iran.
4 Assistant Professor, Department of Physical Education and Sports Science, Faculty of Social Sciences, Imam Khomeini International University, Qazvin, Iran.
5 Professor, Department of Pathobiology, Faculty of Veterinary Medicine, Tabriz Medical Sciences, Islamic Azad University, Tabriz, Iran.
چکیده [English]

Aim:      Parkinson's disease is a neurodegenerative disease characterized by the destruction of dopaminergic neurons in the substantia nigra region of the brain. Alpha-synuclein is a protein that forms plaques called Lewy bodies in Parkinson's disease and is considered the main cause of brain tissue damage. The purpose of the present study was to determine the effect of an intense interval training period and acetyl-L-carnitine (ALC) supplementation on alpha-synuclein and thioredoxin (TRX) protein levels in the brains of 6-hydroxydopamine-induced parkinsonian rats. Research method: The statistical population of this study included 36 Wistar male rats, which were randomly divided into 6 equal groups: healthy control group, sham surgery group, Parkinson's control group, Parkinson's exercise group, Parkinson's supplement group, Parkinson's exercise and supplement group. This experimental research was carried out during 12 weeks of training and the drug receiving groups received ALC supplement once a day for 12 weeks with a dose of 100 mg/kg by gavage. Behavioral tests were performed to confirm the creation of the Parkinsonian model. Tissue samples were obtained 48 hours after the last exercise program. Results: The findings showed that after 12 weeks of HIIT training and ALC consumption, there was a significant difference in TRX (P=0.001) and alpha-synuclein (P=0.001) values between the study groups. The results of the follow-up test showed that the values of TRX and alpha-synuclein in the exercise+supplement group increased (P=0.001) and decreased (P=0.002) respectively, compared to the Parkinson's control group. There was no significant difference in the values of alpha-synuclein in the training (p=0.114) and supplement (p=0.325) groups compared to the Parkinson's control group. Conclusion: Intense intermittent exercise with ALC supplement may be effective in improving cell damage and function of Parkinson's patients by modulating some oxidative regulatory pathways, including increasing TRX antioxidant enzyme and reducing brain tissue alpha-synuclein accumulation.
  

کلیدواژه‌ها [English]

  • Intense interval training
  • thioredoxin
  • alpha-synuclein
  • 6-hydroxydopamine
  • Parkinson

مراجع

  1. Balestrino R, Schapira AJEjon. Parkinson disease. 2020;27(1):27-42.
  2. Mohamadpour F, Aflakseir A, Mohamadi N, Hadianfard HJPPR. Analysis of components of meaning of life in elderly. 2021;7(1):1-18. [In persian]
  3. Piccinini E. Neurotrophic factors GDNF and NRTN: from basic properties to clinical trials. 2014.
  4. Nocker M, Seppi K, Donnemiller E, Virgolini I, Wenning GK, Poewe W, et al. Progression of dopamine transporter decline in patients with the Parkinson variant of multiple system atrophy: a voxel-based analysis of [123 I] β-CIT SPECT. 2012;39:1012-20.
  5. Subramaniam SR, Chesselet M-F. Mitochondrial dysfunction and oxidative stress in Parkinson's disease. Progress in neurobiology. 2013;106:17-32.
  6. Mor DE, Ugras SE, Daniels MJ, Ischiropoulos H. Dynamic structural flexibility of α-synuclein. Neurobiology of Disease. 2016;88:66-74.
  7. Snead D, Eliezer DJEn. Alpha-synuclein function and dysfunction on cellular membranes. 2014;23(4):292.
  8. Goldstein DS, Holmes C, Kopin IJ, Sharabi YJTJoCI. Intra-neuronal vesicular uptake of catecholamines is decreased in patients with Lewy body diseases. 2011;121(8):3320-30.
  9. Salim SJJoP, Therapeutics E. Oxidative stress and the central nervous system. 2017;360(1):201-5.
  10. Awan MUN, Yan F, Mahmood F, Bai L, Liu J, Bai JJA, et al. The functions of thioredoxin 1 in neurodegeneration. 2022;36(13):1023-36.
  11. Liu Z, Wang F, Guo Y, Cui R, Wang J, Wang DJNL. Protective effect of thioredoxin reductase 1 in Parkinson’s disease. 2021;741:135457.
  12. Anstrom KK, Schallert T, Woodlee MT, Shattuck A, Roberts DCJBbr. Repetitive vibrissae-elicited forelimb placing before and immediately after unilateral 6-hydroxydopamine improves outcome in a model of Parkinson's disease. 2007;179(2):183-91.
  13. Choe M-A, Koo B-S, An GJ, Jeon SJTKJoP, Society POJotKP, Pharmacology tKSo. Effects of treadmill exercise on the recovery of dopaminergic neuron loss and muscle atrophy in the 6-ohda lesioned parkinson's disease rat model. 2012;16(5):305.
  14. Oliveira NR, Marques SO, Luciano TF, Pauli JR, Moura LP, Caperuto E, et al. Treadmill training increases SIRT-1 and PGC-1α protein levels and AMPK phosphorylation in quadriceps of middle-aged rats in an intensity-dependent manner. 2014;2014.
  15. Pourrazi H, Asgharpour-Arshad M, Gholami F, Abbasi SJG, Cell, Tissue. Effect of high-intensity interval training on apoptotic gene expression in rat myocardial tissue. 2020;7(2).
  16. Wadley A, Chen Y-W, Bennett S, Lip GY, Turner JE, Fisher JP, et al. Monitoring changes in thioredoxin and over-oxidised peroxiredoxin in response to exercise in humans. 2015;49(3):290-8.
  17. Lappalainen Z, Lappalainen J, Oksala NK, Laaksonen DE, Khanna S, Sen CK, et al. Diabetes impairs exercise training-associated thioredoxin response and glutathione status in rat brain. 2009;106(2):461-7.
  18. Coşkun Ş, Gönül B, Güzel NA, Balabanlí BJM, biochemistry c. The effects of vitamin C supplementation on oxidative stress and antioxidant content in the brains of chronically exercised rats. 2005;280:135-8.
  19. Almeida MF, Silva CM, Chaves RS, Lima NC, Almeida RS, Melo KP, et al. Effects of mild running on substantia nigra during early neurodegeneration. 2018;36(12):1363-70.
  20. chul Jang Y, Hwang DJ, Koo JH, Um HS, Lee NH, Yeom DC, et al. Association of exercise-induced autophagy upregulation and apoptosis suppression with neuroprotection against pharmacologically induced Parkinson's disease. 2018;22(1):1.
  21. Daniele S, Pietrobono D, Fusi J, Iofrida C, Chico L, Petrozzi L, et al. α-Synuclein aggregates with β-amyloid or tau in human red blood cells: correlation with antioxidant capability and physical exercise in human healthy subjects. 2018;55:2653-75.
  22. Zhou W, Barkow JC, Freed CRJPo. Running wheel exercise reduces α-synuclein aggregation and improves motor and cognitive function in a transgenic mouse model of Parkinson's disease. 2017;12(12):e0190160.
  23. Zigmond MJ, Smeyne RJJP, disorders r. Exercise: is it a neuroprotective and if so, how does it work? 2014;20:S123-S7.
  24. Abdul HM, Calabrese V, Calvani M, Butterfield DA. Acetyl‐L‐carnitine‐induced up‐regulation of heat shock proteins protects cortical neurons against amyloid‐beta peptide 1–42‐mediated oxidative stress and neurotoxicity: Implications for Alzheimer's disease. Journal of neuroscience research. 2006;84(2):398-408.
  25. Kobayashi S, Iwamoto M, Kon K, Waki H, Ando S, Tanaka Y. Acetyl‐l‐carnitine improves aged brain function. Geriatrics & gerontology international. 2010;10:S99-S106.
  26. Hatami H, Dehghan GJJoABS. The Effect of Ethanolic The effect of ethanolic extract of Saffron (Crocus sativus L.) on improving the spatial memory parameters in the experimental models of Parkinson disease in male rats. 2015;5(4):534-41. [In persian]
  27. Barhwal K, Hota S, Jain V, Prasad D, Singh S, Ilavazhagan GJN. Acetyl-l-carnitine (ALCAR) prevents hypobaric hypoxia–induced spatial memory impairment through extracellular related kinase–mediated nuclear factor erythroid 2-related factor 2 phosphorylation. 2009;161(2):501-14.
  28. Bielefeld EC, Coling D, Chen G-D, Henderson DJJoNRiB. Multiple dosing strategies with acetyl L-carnitine (ALCAR) fail to alter age-related hearing loss in the Fischer 344/NHsd rat. 2008;7:1-5.
  29. Roghani M, Behzadi G, Baluchnejadmojarad TJP, behavior. Efficacy of elevated body swing test in the early model of Parkinson's disease in rat. 2002;76(4-5):507-10.
  30. Paxinos G, Watson C. The brain in stereotaxic coordinates. New York. Academic Press; 2014.
  31. Landers MR, Kinney JW, van Breukelen F. Forced exercise before or after induction of 6-OHDA-mediated nigrostriatal insult does not mitigate behavioral asymmetry in a hemiparkinsonian rat model. Brain research. 2014;1543:263-70.
  32. Henderson KK, Wagner H, Favret F, Britton SL, Koch LG, Wagner PD, et al. Determinants of maximal O2 uptake in rats selectively bred for endurance running capacity. 2002;93(4):1265-74.
  33. Thomas C, Bishop D, Moore-Morris T, Mercier JJAJoP-E, Metabolism. Effects of high-intensity training on MCT1, MCT4, and NBC expressions in rat skeletal muscles: influence of chronic metabolic alkalosis. 2007;293(4):E916-E22.
  34. Liu Z, Jing Y, Yin J, Mu J, Yao T, Gao LJNrr. Downregulation of thioredoxin reductase 1 expression in the substantia nigra pars compacta of Parkinson's disease mice. 2013;8(35):3275-83.
  35. Lopert P, Day BJ, Patel MJPo. Thioredoxin reductase deficiency potentiates oxidative stress, mitochondrial dysfunction and cell death in dopaminergic cells. 2012;7(11):e50683.
  36. Schober AJC, research t. Classic toxin-induced animal models of Parkinson’s disease: 6-OHDA and MPTP. 2004;318(1):215-24.
  37. Metin G, Kucur M, İşman F, Altan M, Mengi M, Çakar L, et al. The effect of regular training with vitamin E supplementation on the thioredoxine system in rats. 2010;2010(2).
  38. Hamakawa M, Ishida A, Tamakoshi K, Shimada H, Nakashima H, Noguchi T, et al. Repeated short-term daily exercise ameliorates oxidative cerebral damage and the resultant motor dysfunction after transient ischemia in rats. 2013;53(1):8-14.
  39. Jahani G, Firoozrai M, Matin Homaee H, Tarverdizadeh B, Azarbayjani M, Movaseghi G, et al. The effect of continuous and regular exercise on erytrocyte antioxidative enzymes activity and stress oxidative in young soccer players. 2010;17(74):22-32. [In persian]
  40. Holmgren AJA, signaling r. Antioxidant function of thioredoxin and glutaredoxin systems. 2000;2(4):811-20.
  41. Sokouti H, Mohajeri D, Nourazar MAJPR.6-Hydroxydopamine-Induced Neurotoxicity in Rat Model of Parkinson’s Disease: Is Reversed via Anti-Oxidative Activities of Curcumin and Aerobic Exercise Therapy. 2022;71(4):551.
  42. Lehmensiek V, Tan E-M, Liebau S, Lenk T, Zettlmeisl H, Schwarz J, et al. Dopamine transporter-mediated cytotoxicity of 6-hydroxydopamine in vitro depends on expression of mutant α-synucleins related to Parkinson's disease. 2006;48(5):329-40.
  43. Atalay M, Oksala NK, Laaksonen DE, Khanna S, Nakao C, Lappalainen J, et al. Exercise training modulates heat shock protein response in diabetic rats. 2004;97(2):605-11.
  44. Tian X, Zhou N, Yuan J, Lu L, Zhang Q, Wei M, et al. Heat shock transcription factor 1 regulates exercise‐induced myocardial angiogenesis after pressure overload via HIF‐1α/VEGF pathway. 2020;24(3):2178-88.
  45. Kim E, Wang B, Sastry N, Masliah E, Nelson PT, Cai H, et al. NEDD4-mediated HSF1 degradation underlies α-synucleinopathy. 2016;25(2):211-22.
  46. Peer ME, Fallahmohammadi Z, Akbari AJMO. The effect of progressive endurance training and extract of black winter truffle on proteins levels and expression of hippocampus α-synuclein and HSF1 in the healthy and diabetic rats. 2023;17:100232.
  47. Calabrese V, Colombrita C, Sultana R, Scapagnini G, Calvani M, Butterfield D, et al. Redox modulation of heat shock protein expression by acetylcarnitine in aging brain: relationship to antioxidant status and mitochondrial function. 2006;8(3-4):404-16.
  48. Calabrese V, Ravagna A, Colombrita C, Scapagnini G, Guagliano E, Calvani M, et al. Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: involvement of the transcription factor Nrf2. 2005;79(4):509-21.
مطالعات کاربردی تندرستی در فیزیولوژی ورزش
دوره 12، شماره 1
فروردین 1404
صفحه 81-94

فایل ها

سابقه مقاله

  • تاریخ دریافت: 13 اسفند 1402
  • تاریخ بازنگری: 12 تیر 1403
  • تاریخ پذیرش: 12 تیر 1403

هم رسانی

ارجاع به این مقاله

آمار