تأثیر چهار هفته فعالیت هوازی در آب بر میزان بهبود بالینی و پروتئین نوروگلین-1 در بافت مغز مدل حیوانی Multiple Sclerosis از طریق القای Experimental Autoimmune Encephalomyelitis (EAE)

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 دانشجوی دکتری، گروه فیزیولوژی ورزشی، دانشکده‌ی تربیت بدنی و علوم ورزشی، دانشگاه خوارزمی، تهران، ایران

2 دانشیار، گروه فیزیولوژی ورزشی، دانشکده‌ی تربیت بدنی و علوم ورزشی، دانشگاه خوارزمی، تهران، ایران

3 استادیار، گروه ایمنی‌شناسی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی جندی‌شاپور اهواز، اهواز، ایران

4 استاد، گروه تربیت بدنی، دانشکده‌ی علوم انسانی، دانشگاه تربیت مدرس، تهران، ایران

5 استاد، گروه فیزیولوژی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی جندی‌شاپور اهواز، اهواز، ایران

چکیده

مقدمه: هدف از این پژوهش، تعیین تأثیر چهار هفته فعالیت هوازی در آب بر میزان بهبود بالینی و پروتئین نوروگلین-1 در بافت مغز مدل حیوانی Multiple sclerosis (MS) از طریق القای Experimental autoimmune encephalomyelitis (EAE) بود.روش‌ها: 80 سر موش‌ سوری ماده با نژاد C57BL/6 و سن 12-10 هفته و وزن 2 ± 20 گرم به 8 گروه 10تایی (سالم شاهد، سالم شنا، MS شاهد، MS اینترفرون، MS شنا، MS اینترفرون شنا، MS شاهد تزریق، MS شاهد شنا و تزریق) تقسیم شدند. جهت القای EAE، ابتدا 300 میکروگرم (55-35) Myelin oligodendrocyte glycoprotein (MOG) در حجم 100 میکرولیتر Phosphate buffered saline (PBS) با Complete Freund's adjuvant (CFA) مخلوط و به صورت زیر جلدی تزریق شد. هم‌زمان با تزریق اول و 48 ساعت بعد از آن، 300 نانوگرم سم سیاه‌سرفه (Pertussis toxin یا PT) به صورت داخل صفاقی تزریق شد. موش‌های مصرف کننده‌ی دارو به صورت اینترفرون بتا، از هفته‌ی اول پس از شروع درمان، روزانه به میزان 150 واحد بین‌المللی/گرم از این دارو را به صورت زیر جلدی دریافت کردند. علایم بالینی و وزن موش‌ها روزانه بررسی و ثبت شد. برای گروه‌های تمرین، روزانه 30 دقیقه به مدت 4 هفته، هفته‌ای 5 جلسه، فعالیت هوازی در محفظه‌ی شنا اجرا شد. از سیستم نمره‌دهی استاندارد برای ارزیابی بالینی و از روش Enzyme-linked immunosorbent assay (ELISA) برای اندازه‌گیری پروتئین نوروگلین-1 استفاده گردید. داده‌های به دست آمده، با استفاده از آزمون One-way ANOVA تجزیه و تحلیل شد.یافته‌ها: تأثیر فعالیت ورزشی شنا بر MS، به طور تقریبی یکسان با تأثیر اینترفرون بر MS بود. میزان افزایش نوروگلین-1 در گروه MS شنا نسبت به گروه MS اینترفرون بیشتر بود.نتیجه‌گیری: تمرین هوازی شنا، به احتمال زیاد می‌تواند از طریق افزایش نوروگلین-1 به بازسازی میلین یا کاهش سرعت تخریب میلین کمک کند و از این طریق، به بهبود بالینی بیماران مبتلا به MS منجر شود.

کلیدواژه‌ها

عنوان مقاله [English]

The Effect of a Four-week Aerobic Activity in Water on the Extent of Clinical Improvement and Neuregulin-1 (NRG1) Protein in the Brain Tissue of Animal Model of Multiple Sclerosis (MS) via Inducing Experimental Autoimmune Encephalomyelitis (EAE)

نویسندگان [English]

  • Seyed Rouhollah Mousavi 1
  • Hamid Rajabi 2
  • Ata Allah Ghadiri 3
  • Reza Gharakhanlou 4
  • Alireza Sarkaki 5
1 PhD Student, Department of Exercise Physiology, School of Physical Education and Sports Sciences, Kharazmi University, Tehran, Iran
2 Associate Professor, Department of Exercise Physiology, School of Physical Education and Sports Sciences, Kharazmi University, Tehran, Iran
3 Assistant Professor, Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4 Professor, Department of Physical Education, School of Humanities, Tarbiat Modares University, Tehran, Iran
5 Professor, Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
چکیده [English]

Background: This study was conducted to investigate the effect of a four-week aerobic physical activity in water on the extent of clinical improvement and amount of neuregulin-1 (NRG1) protein in the brain tissue of animal model of multiple sclerosis (MS) via inducing experimental autoimmune encephalomyelitis (EAE).Methods: To this end, a total number of 80 female Syrian mice from the race of C57BL/6, aging 10 to 12 weeks and weighing 20 ± 2 gram were divided into eight groups of 10, namely, control, swimming, MS, MS + swimming, MS + interferon beta (INF-β), MS + solvent, and MS + solvent + swimming environment. For induction of EAE, 300 μg (35-55) myelin oligodendrocyte glycoprotein (MOG) was first mixed in 100 μl phosphate buffered saline (PBS) with complete Freund's adjuvant (CFA) and injected subcutaneously (SC). At the time of injection and after 48 hours, 300 ng pertussis toxin was diluted in PBS and injected intraperitoneally (IP). During a week after the treatment, mice recieving the drug in form of intraperitoneal received 150 IU/g of the drug per day. Clinical symptoms and the mice's weights were recorded every day. Physical activity group did the aerobic activities for four weeks, five sessions a week, 30 minutes each session. Standard scoring system was used for clinical check and enzyme-linked immunosorbent assay (ELISA) was applied to measure NRG1 protein. Data analysis was done using one-way ANOVA.Findings: The effect of physical activity in water on treatment of multiple sclerosis was the same as that of interferon. The amount of rise in NRG1 protein in swimming group was more than that of the interferon group.Conclusion: Aerobic swimming exercises could probably help remyelination by increasing the amount of NRG1 protein and lowering the speed of myelin destruction, hence, helping the clinical improvement in patients with multiple sclerosis.

کلیدواژه‌ها [English]

  • Neuregulin-1
  • Aerobic exercises
  • Multiple Sclerosis

مراجع

  1. Bradley WG, Daroff RB, Fenichel GM, Jankovic J. Neurology in clinical practice. 4th ed. New York, NY: Butterworth-Heinemann; 2003.
  2. Ghaem H, Borhani HA, Jafari P, Nikseresht AR. Validity and reliability of the Persian version of the multiple sclerosis quality of life questionnaire. Neurol India 2007; 55(4): 369-75.
  3. Ninety thousand Iranians annual incidence of MS [Online]. [cited 2015]; Available from: URL: http://www.imna.ir/fa/doc/interview/100981/75
  4. Karimi A, Delpisheh A, Ashtari F, Sayehmiri K, Meamar R. The relationship between the amount of radiation, relative humidity, and temperature with the risk of multiple sclerosis in Isfahan Province, Iran, during the years 2001-2014. J Isfahan Med Sch 2017; 35(427): 434-9. [In Persian].
  5. Nakahara J, Maeda M, Aiso S, Suzuki N. Current concepts in multiple sclerosis: Autoimmunity versus oligodendrogliopathy. Clin Rev Allergy Immunol 2012; 42(1): 26-34.
  6. Cerasa A, Tongiorgi E, Fera F, Gioia MC, Valentino P, Liguori M, et al. The effects of BDNF Val66Met polymorphism on brain function in controls and patients with multiple sclerosis: An imaging genetic study. Behav Brain Res 2010; 207(2): 377-86.
  7. Thone J, Ellrichmann G. Oral available agents in the treatment of relapsing remitting multiple sclerosis: An overview of merits and culprits. Drug Healthc Patient Saf 2013; 5: 37-47.
  8. Hadgkiss EJ, Jelinek GA, Weiland TJ, Rumbold G, Mackinlay CA, Gutbrod S, et al. Health-related quality of life outcomes at 1 and 5 years after a residential retreat promoting lifestyle modification for people with multiple sclerosis. Neurol Sci 2013; 34(2): 187-95.
  9. Zaheer S, Wu Y, Sahu SK, Zaheer A. Suppression of neuro inflammation in experimental autoimmune encephalomyelitis by glia maturation factor antibody. Brain Res 2011; 1373: 230-9.
  10. Viehover A, Miller RH, Park SK, Fischbach G, Vartanian T. Neuregulin: An oligodendrocyte growth factor absent in active multiple sclerosis lesions. Dev Neurosci 2001; 23(4-5): 377-86.
  11. Nave KA, Salzer JL. Axonal regulation of myelination by neuregulin 1. Curr Opin Neurobiol 2006; 16(5): 492-500.
  12. Guma A, Martinez-Redondo V, Lopez-Soldado I, Canto C, Zorzano A. Emerging role of neuregulin as a modulator of muscle metabolism. Am J Physiol Endocrinol Metab 2010; 298(4): E742-E750.
  13. Odiete O, Hill MF, Sawyer DB. Neuregulin in cardiovascular development and disease. Circ Res 2012; 111(10): 1376-85.
  14. Ennequin G, Boisseau N, Caillaud K, Chavanelle V, Gerbaix M, Metz L, et al. Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats. J Physiol 2015; 593(12): 2665-77.
  15. Murray PS, Holmes PV. An overview of brain-derived neurotrophic factor and implications for excitotoxic vulnerability in the hippocampus. Int J Pept 2011; 2011: 654085.
  16. White LJ, McCoy SC, Castellano V, Gutierrez G, Stevens JE, Walter GA, et al. Resistance training improves strength and functional capacity in persons with multiple sclerosis. Mult Scler 2004; 10(6): 668-74.
  17. Dalgas U, Stenager E, Ingemann-Hansen T. Multiple sclerosis and physical exercise: recommendations for the application of resistance-, endurance- and combined training. Mult Scler 2008; 14(1): 35-53.
  18. Motl RW. Lifestyle physical activity in persons with multiple sclerosis: the new kid on the MS block. Mult Scler 2014; 20(8): 1025-9.
  19. Yoon H, Kleven A, Paulsen A, Kleppe L, Wu J, Ying Z, et al. Interplay between exercise and dietary fat modulates myelinogenesis in the central nervous system. Biochim Biophys Acta 2016; 1862(4): 545-55.
  20. Lundgaard I, Luzhynskaya A, Stockley JH, Wang Z, Evans KA, Swire M, et al. Neuregulin and BDNF induce a switch to NMDA receptor-dependent myelination by oligodendrocytes. PLoS Biol 2013; 11(12): e1001743.
  21. Brosnan CF, Cannella B, Battistini L, Raine CS. Cytokine localization in multiple sclerosis lesions: correlation with adhesion molecule expression and reactive nitrogen species. Neurology 1995; 45(6 Suppl 6): S16-S21.
  22. Begolka WS, Vanderlugt CL, Rahbe SM, Miller SD. Differential expression of inflammatory cytokines parallels progression of central nervous system pathology in two clinically distinct models of multiple sclerosis. J Immunol 1998; 161(8): 4437-46.
  23. Teixeira SA, Castro GM, Papes F, Martins ML, Rogerio F, Langone F, et al. Expression and activity of nitric oxide synthase isoforms in rat brain during the development of experimental allergic encephalomyelitis. Brain Res Mol Brain Res 2002; 99(1): 17-25.
  24. Bernardes D, Brambilla R, Bracchi-Ricard V, Karmally S, Dellarole A, Carvalho-Tavares J, et al. Prior regular exercise improves clinical outcome and reduces demyelination and axonal injury in experimental autoimmune encephalomyelitis. J Neurochem 2016; 136(Suppl 1): 63-73.
  25. Fitzgerald DC, Fonseca-Kelly Z, Cullimore ML, Safabakhsh P, Saris CJ, Zhang GX, et al. Independent and interdependent immunoregulatory effects of IL-27, IFN-beta, and IL-10 in the suppression of human Th17 cells and murine experimental autoimmune encephalomyelitis. J Immunol 2013; 190(7): 3225-34.
  26. Skihar V, Silva C, Chojnacki A, Doring A, Stallcup WB, Weiss S, et al. Promoting oligodendrogenesis and myelin repair using the multiple sclerosis medication glatiramer acetate. Proc Natl Acad Sci USA 2009; 106(42): 17992-7.
  27. Thornton EW, Tedman S, Rigby S, Bashforth H, Young C. Worries and concerns of patients with multiple sclerosis: Development of an assessment scale. Mult Scler 2006; 12(2): 196-203.
  28. Florindo M. Inflammatory cytokines and physical activity in multiple sclerosis. ISRN Neurol 2014; 2014: 151572.
  29. Canto C, Chibalin AV, Barnes BR, Glund S, Suarez E, Ryder JW, et al. Neuregulins mediate calcium-induced glucose transport during muscle contraction. J Biol Chem 2006; 281(31): 21690-7.
  30. Scott JM, Lakoski S, Mackey JR, Douglas PS, Haykowsky MJ, Jones LW. The potential role of aerobic exercise to modulate cardiotoxicity of molecularly targeted cancer therapeutics. Oncologist 2013; 18(2): 221-31.
مجله دانشکده پزشکی اصفهان
دوره 35، شماره 447 - شماره پیاپی 447
مهر و آبان 1396
صفحه 1233-1241

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سابقه مقاله

  • تاریخ دریافت: 14 مرداد 1396
  • تاریخ بازنگری: 11 آبان 1403
  • تاریخ پذیرش: 17 فروردین 1401

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