تأثیر یک دوره تمرین ورزشی مقاومتی با شدت بالا بر سطوح اینترلوکین- 10، Tumor necrosis factor-alpha (TNF-α) و Brain-derived neurotrophic factor (BDNF) در مغز رت‌های Lewis مبتلا به آنسفالومیلیت خود ایمن تجربی

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 دانشجوی دکتری، گروه فیزیولوژی ورزشی، دانشکده‌ی علوم ورزشی، دانشگاه مازندران، بابلسر، ایران

2 دانشیار، گروه فیزیولوژی ورزشی، دانشکده‌ی علوم ورزشی، دانشگاه مازندران، بابلسر، ایران

3 استادیار، گروه بافت‌شناسی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی بابل، بابل، ایران

چکیده

مقدمه: Multiple sclerosis (MS)، بیماری التهابی دمیلینه کننده‌ی مزمن Central nervous system (CNS) است. واکنش التهابی با تنظیم افزایشی انواعی از سیتوکاین‌ها در ضایعات MS همبستگی دارد. هدف از انجام این تحقیق، بررسی تأثیر برنامه‌ی ورزشی مقاومتی با شدت بالا در پیش‌گیری از بیماری آنسفالومیلیت خود ایمنی (Experimental autoimmune encephalomyelitis یا EAE) (مدلی برای مطالعه‌ی MS) بود.روش‌ها: تمرینات مقاومتی به مدت 6 هفته و 5 روز در هفته انجام شد. شروع برنامه‌ی تمرینی با بار معادل ۵۰ درصد وزن بدن رت بود. حیوانات در دو جلسه‌ی اول، 10-۸ تکرار (بالا رفتن از نردبان) را با فواصل استراحت ۲ دقیقه‌ای انجام دادند. رت‌ها با نخاع خوکچه‌ی هندی و Complete Freund's adjuvant ایمونیزه شدند. روند بیماری و تغییرات وزن رت‌ها روزانه مورد ارزیابی قرار گرفت. مدل آنسفالومیلیت خود ایمنی در انتهای هفته‌ی ششم تمرینات القا شد.یافته‌ها: تمرین مقاومتی در رت‌های ماده‌ی نژاد Lewis مبتلا به آنسفالومیلیت خود ایمنی، منجر به کاهش معنی‌دار Tumor necrosis factor alpha (TNF-α) (001/0 = P) و افزایش معنی‌دار اینترلوکین- 10 (Interleukin-10 یا IL-10) (001/0 = P) شد، اما تغییر معنی‌داری در عامل مشتق شده از مغز (Brain-derived neurotrophic factor یا BDNF) ایجاد نکرد (055/0 = P). همچنین، علایم بالینی در رت‌های تمرین کرده با تأخیر ظاهر شد.نتیجه‌گیری: با توجه به نتایج، به نظر می‌رسد تمرینات مقاومتی با مدت و شدت لازم موجب تأخیر در بروز و کاهش شدت علایم بالینی، عدم تغییر BDNF، کاهش TNF-α و افزایش IL-10 در رت‌های Lewis مبتلا به آنسفالومیلیت خود ایمنی می‌شود.

کلیدواژه‌ها


عنوان مقاله [English]

The Effect of High-Intensity Resistance Exercise Period on the Levels of Interleukin-10 (IL-10), Tumor Necrosis Factor-Alpha (TNF-α), and Brain-Derived Neurotrophic Factor (BDNF) in the Brain of Lewis Rats with Experimental Autoimmune Encephalomyelitis

نویسندگان [English]

  • Seyed Mojtaba Hosseini 1
  • Zia Fallah-Mohammadi 2
  • Farideh Feizi 3
1 PhD Student, Department of Exercise Physiology, School of Sport Sciences, University of Mazandaran, Babolsar, Iran
2 Associate Professor, Department of Exercise Physiology, School of Sport Sciences, University of Mazandaran, Babolsar, Iran
3 Assistant Professor, Department of Histology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
چکیده [English]

Background: Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). There is a correlation between up-regulation of a variety of cytokines with inflammatory reactions in multiple sclerosis lesions. This study aimed to investigate the effects of high-intensity resistance exercise program on prevention of experimental autoimmune encephalomyelitis (EAE) (a model for studying multiple sclerosis).Methods: Resistance exercises were performed for 6 weeks, 5 days a week. Training program started with 50% of rats' body weight. In the first session, animals performed 8 to 10 repetitions (up the ladder) with 2-minute rest intervals. Rats were immunized with spinal cord and complete adjuvant of guinea pigs. Disease process and changes in rats' weights were measured every day. Experimental autoimmune encephalomyelitis model was induced at the end of the sixth week of training.Findings: Resistance training in Lewis female rats with experimental autoimmune encephalomyelitis resulted in a significant reduction in tumor necrosis factor-alpha (TNF-α) (P = 0.001) and a significant increase in interleukin-10 (IL-10) (P = 0.001). However, it did not cause significant changes in Brain-Derived Neurotrophic Factor (BDNF) (P = 0.055). In addition, clinical symptoms in exercised rats were postponed.Conclusion: Regarding the results, it appears that resistance exercises with necessary duration and intensity delay the onset, reduce the severity of clinical symptoms, and decrease TNF-α, increase IL-10, with no change in BDNF, in Lewis rats with experimental autoimmune encephalomyelitis.

کلیدواژه‌ها [English]

  • Multiple Sclerosis
  • Cytokines
  • Resistance Training
  • Experimental autoimmune encephalomyelitis
  1. Moghadasi M, Edalatmanesh MA, Moeini A, Nematollahzadeh Mahani MS. Effects of eight weeks resistance training on brain derived neurotrophic factor in female patients with multiple sclerosis. Koomesh 2015; 17(1): 152-9. [In Persian].
  2. Kjolhede T, Dalgas U, Gade AB, Bjerre M, Stenager E, Petersen T, et al. Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis. Scand J Med Sci Sports 2016; 26(7): 824-34.
  3. Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi J, et al. Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 2002; 87(4): 728-34.
  4. Azoulay D, Vachapova V, Shihman B, Miler A, Karni A. Lower brain-derived neurotrophic factor in serum of relapsing remitting MS: reversal by glatiramer acetate. J Neuroimmunol 2005; 167(1-2): 215-8.
  5. Bernardes D, Oliveira-Lima OC, Silva TV, Faraco CC, Leite HR, Juliano MA, et al. Differential brain and spinal cord cytokine and BDNF levels in experimental autoimmune encephalomyelitis are modulated by prior and regular exercise. J Neuroimmunol 2013; 264(1-2): 24-34.
  6. Huang AM, Jen CJ, Chen HF, Yu L, Kuo YM, Chen HI. Compulsive exercise acutely upregulates rat hippocampal brain-derived neurotrophic factor. J Neural Transm (Vienna) 2006; 113(7): 803-11.
  7. Gomez-Pinilla F, Vaynman S, Ying Z. Brain-derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition. Eur J Neurosci 2008; 28(11): 2278-87.
  8. Waschbisch A, Wenny I, Tallner A, Schwab S, Pfeifer K, Maurer M. Physical activity in multiple sclerosis: a comparative study of vitamin D, brain-derived neurotrophic factor and regulatory T cell populations. Eur Neurol 2012; 68(2): 122-8.
  9. Castellano V, White LJ. Serum brain-derived neurotrophic factor response to aerobic exercise in multiple sclerosis. J Neurol Sci 2008; 269(1-2): 85-91.
  10. Castellano V, Patel DI, White LJ. Cytokine responses to acute and chronic exercise in multiple sclerosis. J Appl Physiol (1985) 2008; 104(6): 1697-702.
  11. TNF-α: a paradigm of paradox and complexity in multiple sclerosis and its animal models. The Open Autoimmunity Journal 2010; 2: 160-70.
  12. Sharief MK, Hentges R. Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis. N Engl J Med 1991; 325(7): 467-72.
  13. Kordi M, Anooshe L, Khodadade S, Maghsodi N, Sanglachi B, Hemmatinafar B. Comparing the effect of three methods of combined training on serum levels of ghrelin, pro and anti-inflammatory cytokines in multiple sclerosis (MS) patients. J Zanjan Univ Med Sci 2014; 22 (91): 39-51. [In Persian].
  14. Maghsodi N, Khosravi N, Ravasi AA. The effect of a period of selected training (aerobic and resistance) on some cytokines in male and female patients with multiple sclerosis. Sport Biosciences 2011; (10): 5-23. [In Persian].
  15. Patel DI, White LJ. Effect of 10-day forced treadmill training on neurotrophic factors in experimental autoimmune encephalomyelitis. Appl Physiol Nutr Metab 2013; 38(2): 194-9.
  16. Wens I, Hansen D, Verboven K, Deckx N, Kosten L, Stevens AL, et al. Impact of 24 weeks of resistance and endurance exercise on glucose tolerance in persons with multiple sclerosis. Am J Phys Med Rehabil 2015; 94(10 Suppl 1): 838-47.
  17. Safarzadeh A, Hajizadeh Rostami M, Talebi Garakani E, Fathi R. The effects of progressive resistance training on serum omentin-1 and lipid profile of rats. Sport Biosciences 2014: (22): 287-300. [In Persian].
  18. Yaghmaei P, Nabiuni M, Mahdavi M, Mehrvarz T, Nazari Z. The effects of honey bee venom on the serum interleukin 6 level in EAE Lewis rats a model for the study of multiple sclerosis. Pejouhandeh 2013; 18(2): 69-75. [In Persian].
  19. Pryor WM, Freeman KG, Larson RD, Edwards GL, White LJ. Chronic exercise confers neuroprotection in experimental autoimmune encephalomyelitis. J Neurosci Res 2015; 93(5): 697-706.
  20. Briken S, Rosenkranz SC, Keminer O, Patra S, Ketels G, Heesen C, et al. Effects of exercise on Irisin, BDNF and IL-6 serum levels in patients with progressive multiple sclerosis. J Neuroimmunol 2016; 299: 53-8.
  21. Motl RW, Sandroff BM. Benefits of exercise training in multiple sclerosis. Curr Neurol Neurosci Rep 2015; 15(9): 62.
  22. Casado MA. The effect of 12 weeks high-intensity interval - and resistance training on mobility and quality of life in multiple sclerosis. Hasselt, Belgium: University of Hasselt; 2016.
  23. Wens I, Keytsman C, Deckx N, Cools N, Dalgas U, Eijnde BO. Brain derived neurotrophic factor in multiple sclerosis: effect of 24 weeks endurance and resistance training. Eur J Neurol 2016; 23(6): 1028-35.
  24. Ang ET, Wong PT, Moochhala S, Ng YK. Cytokine changes in the horizontal diagonal band of Broca in the septum after running and stroke: a correlation to glial activation. Neuroscience 2004; 129(2): 337-47.
  25. Kierkegaard M, Lundberg IE, Olsson T, Johansson S, Ygberg S, Opava C, et al. High-intensity resistance training in multiple sclerosis - An exploratory study of effects on immune markers in blood and cerebrospinal fluid, and on mood, fatigue, health-related quality of life, muscle strength, walking and cognition. J Neurol Sci 2016; 362: 251-7.
  26. Golzari Z, Shabkhiz F, Soudi S, Kordi MR, Hashemi SM. Combined exercise training reduces IFN-gamma and IL-17 levels in the plasma and the supernatant of peripheral blood mononuclear cells in women with multiple sclerosis. Int Immunopharmacol 2010; 10(11): 1415-9.
  27. Bezheh N, Soltani M, Khaleghzade H. Effects of aerobic training in water on IL-6 and IL-10 in patients with multiple sclerosis. Evid Basic Care 2014; 4(2): 63-72. [In Persian].
  28. Khalilnezhad A, Zahednasab H, Khodabandehloo H, Mahmoudian E, Azar-Abdar T, Balood M, et al. Diagnostic Biomarkers in Multiple Sclerosi. J Ilam Univ Med Sci 2013; 21(7): 288-311. [In Persian].
  29. Cotman CW, Engesser-Cesar C. Exercise enhances and protects brain function. Exerc Sport Sci Rev 2002; 30(2): 75-9.
  30. Zhu W, Frost EE, Begum F, Vora P, Au K, Gong Y, et al. The role of dorsal root ganglia activation and brain-derived neurotrophic factor in multiple sclerosis. J Cell Mol Med 2012; 16(8): 1856-65.
  31. Fallah-mohammadi Z, Ahmadi-kordasiabi M, Aghasi M. The effect of voluntary exercise on MANF level in the brainstem of Parkinsonian rats induced by 6-Hydroxydopamine. J Birjand Univ Med Sci 2014; 21(2): 179-87. [In Persian].
  32. Sorenson M, Jason L, Peterson J, Herrington J, Mathews H. Brain Derived Neurotrophic Factor is Decreased in Chronic Fatigue Syndrome and Multiple Sclerosis. J Neurol Neurophysiol 2014; S12: S2-013.