تأثیر شش هفته تمرین اجباری و اختیاری پیش‌آماده‌سازی بر بیان برخی مولکول‌های چسبان مؤثر بر نفوذپذیری سد خونی-مغزی در موش‌های ام اس روش EAE

نوع مقاله : علمی - پژوهشی

نویسندگان

دانشکدة تربیت بدنی و علوم ورزشی، دانشگاه تهران، تهران، ایران

چکیده

هدف: حدود 5/2 میلیون نفر در سراسر جهان به مولتیپل اسکلروزیس، بیماری مزمن عصبی-التهابی مغز و نخاع، مبتلا هستند که علت شایع ناتوانی جسمی جدی در جوانان، به‌ویژه زنان است. هدف از این تحقیق بررسی تأثیر فعالیت اختیاری و اجباری پیش از القای EAE بر بیان مقادیر مولکول‌های چسبان (ICAM-1 و VCAM-1) مؤثر بر نفوذپذیری سد خونی-مغزی در موش‌های مادة C57BL/6 است.
روش‌ها: 40 سر موش مادة C57BL/6 با وزن 2±18گرم و سن 1±7 هفته به روش تصادفی ساده به چهار گروه فعالیت اجباری (12n= )، فعالیت اختیاری (12n=)، کنترل EAE (8n=) و کنترل سالم (8n=) تقسیم شدند. برای اجرای فعالیت اجباری، موش‌ها فعالیت شنا را به مدت 30 دقیقه پنج روز در هفته و در طول شش هفته انجام دادند. همچنین برای اجرای فعالیت اختیاری موش‌ها یک ساعت در روز و پنج روز در هفته به مدت شش هفته در قفسی به یک چرخ گردان دسترسی پیدا کردند. پس از اتمام دورة تمرین بیان ژن ICAM-1 و VCAM-1 به روش RT-PCR اندازه‌گیری شد. در تجزیه‌وتحلیل داده‌ها برای تعیین اختلاف داده‌ها در بین گروه‌ها از آزمون تحلیل واریانس یکطرفه و آزمون تعقیبی توکی در سطح معناداری 05/0 P≤  استفاده شد.
نتایج: پنج هفته ثبت علائم بالینی پس از القای EAE تفاوت معناداری بین نمرات دو گروه فعالیت ورزشی و گروه کنترل EAE نشان داد (05/0P<). همچنین بیان مولکول‌های چسبان ICAM-1 و VCAM-1 در دو گروه فعالیت اختیاری و اجباری نسبت به کنترل EAE کاهش معنادار داشتند ( 05/0P<)، اما نسبت به گروه کنترل سالم تفاوت معناداری نداشتند (05/0 P>).
نتیجه‌گیری: به‌نظر می‌رسد دو نوع فعالیت اختیاری و اجباری با کاهش بیان مولکول‌های چسبان ICAM-1 و VCAM-1 سبب کاهش نفوذپذیری سد خونی-مغزی می‌شود.

کلیدواژه‌ها


عنوان مقاله [English]

Effect of six weeks forced and voluntary training before EAE induction on the expression of some adhesive molecules affecting the blood-brain barrier permeability

نویسندگان [English]

  • Mohammad Reza Rahmati
  • Mohammad Reza Kordi
  • Ali Asghar Ravasi
Faculty of Physical Education and Sport Sciences, University of Tehran, Tehran, Iran
چکیده [English]

Purpose: Nearly 2.5 million people worldwide have multiple sclerosis, a chronic neuro-inflammatory disease of the brain and spinal cord that is a common cause of severe physical disability in young people, especially women. Therefore, the aim of this study was to investigate the effect of forced and voluntary training before EAE induction on the expression of adhesive molecule ​​(ICAM-1 and VCAM-1) affecting the blood-brain barrier permeability in C57BL/6 mice.
Methods: Forty female C57BL/6 mice with weight 18 ± 2 g and age 7 ± 1 weeks were randomly divided to four groups of forced training (n = 12), voluntary training (n=12), EAE control (n = 8) and healthy control (n = 8). To perform the forced training, the mice performed swimming for 30 minutes five days/week for  six  weeks. Also to perform the voluntary training, the mice performed running wheel for one hour five days/week for six weeks. After that ICAM-1 and VCAM-1 gene expression were measured by RT-PCR. In data analysis, one-way ANOVA and Tukey's post-hoc test were applied to determine the difference between the groups.
Results: Five weeks recording clinical signs after EAE induction showed a significant difference between the scores of the two training groups and EAE control (P < 0.05). Also, the expression of ICAM-1 and VCAM-1 adhesive molecules significantly decreased in the forced and voluntary groups compared to EAE control (P < 0.05), but the forced and voluntary groups significantly did not differ from the healthy control group (P > 0.05).
Conclusion: The forced and voluntary training appears to reduce the blood-brain barrier permeability by reducing the expression of ICAM-1 and VCAM-1 adhesive molecules.

کلیدواژه‌ها [English]

  • MS disease
  • Multiple Sclerosis
  • ICAM-1
  • VCAM-1
  • blood-brain barrier Integrity
  1. Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nature Reviews Immunology. 2015;15(9):545-58.
  2. Constantinescu CS, Farooqi N, O'Brien K, Gran BJBjop. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). 2011;164(4):1079-106.
  3. Jiang H, Zhang F, Yang J, Han S. Angiopoietin-1 ameliorates inflammation-induced vascular leakage and improves functional impairment in a rat model of acute experimental autoimmune encephalomyelitis. Experimental neurology. 2014;261:245-57.
  4. Wang X-S, Fang H-L, Chen Y, Liang S-S, Zhu Z-G, Zeng Q-Y, et al. Idazoxan reduces blood–brain barrier damage during experimental autoimmune encephalomyelitis in mouse. European journal of pharmacology. 2014;736:70-6.
  5. Souza PS, Gonçalves ED, Pedroso GS, Farias HR, Junqueira SC, Marcon R, et al. Physical exercise attenuates experimental autoimmune encephalomyelitis by inhibiting peripheral immune response and blood-brain barrier disruption. Molecular neurobiology. 2017;54(6):4723-37.
  6. Sonar SA, Shaikh S, Joshi N, Atre AN, Lal G. IFN-γ promotes transendothelial migration of CD4+ T cells across the blood–brain barrier. Immunology and cell biology. 2017;95(9):843.
  7. Seo J-E, Hasan M, Han J-S, Kang M-J, Jung B-H, Kwok S-K, et al. Experimental autoimmune encephalomyelitis and age-related correlations of NADPH oxidase, MMP-9, and cell adhesion molecules: the increased disease severity and blood–brain barrier permeability in middle-aged mice. Journal of neuroimmunology. 2015;287:43-53.
  8. Choi JH, Lee MJ, Jang M, Kim E-J, Shim I, Kim H-J, et al. An oriental medicine, Hyungbangpaedok-San attenuates motor paralysis in an experimental model of multiple sclerosis by regulating the T cell response. PloS one. 2015;10(10):e0138592.
  9. Wang D, Li S-P, Fu J-S, Zhang S, Bai L, Guo L. Resveratrol defends blood-brain barrier integrity in experimental autoimmune encephalomyelitis mice. Journal of neurophysiology. 2016;116(5):2173-9.
  10. Dalgas U, Stenager E. Exercise and disease progression in multiple sclerosis: can exercise slow down the progression of multiple sclerosis? Therapeutic advances in neurological disorders. 2012;5(2):81-95.
  11. Kim T-W, Sung Y-H. Regular exercise promotes memory function and enhances hippocampal neuroplasticity in experimental autoimmune encephalomyelitis mice. Neuroscience. 2017;346:173-81.
  12. 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. Journal of neurochemistry. 2016;136(S1):63-73.
  13. Kawanishi N, Yano H, Yokogawa Y, Suzuki K. Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice. Exercise immunology review. 2010;16.
  14. Limberg JK, Johansson RE, McBride PE, Schrage WG. Increased leg blood flow and improved femoral artery shear patterns in metabolic syndrome after a diet and exercise programme. Clinical physiology and functional imaging. 2014;34(4):282-9.
  15. Palmefors H, DuttaRoy S, Rundqvist B, Börjesson M. The effect of physical activity or exercise on key biomarkers in atherosclerosis–a systematic review. Atherosclerosis. 2014;235(1):150-61.
  16. Morgan JA, Corrigan F, Baune BTJJomp. Effects of physical exercise on central nervous system functions: a review of brain region specific adaptations. 2015;3(1):3.
  17. Gentile A, Musella A, De Vito F, Rizzo FR, Fresegna D, Bullitta S, et al. Immunomodulatory effects of exercise in experimental multiple sclerosis. 2019;10.
  18. Benson C, Paylor JW, Tenorio G, Winship I, Baker G, Kerr BJ. Voluntary wheel running delays disease onset and reduces pain hypersensitivity in early experimental autoimmune encephalomyelitis (EAE). Experimental neurology. 2015;271:279-90.
  19. Jin J-J, Ko I-G, Kim S-E, Shin M-S, Kim S-H, Jee Y-SJJoer. Swimming exercise ameliorates multiple sclerosis-induced impairment of short-term memory by suppressing apoptosis in the hippocampus of rats. 2014;10(2):69.
  20. Liu W, Xue X, Xia J, Liu J, Qi ZJJoad. Swimming exercise reverses CUMS-induced changes in depression-like behaviors and hippocampal plasticity-related proteins. 2018;227:126-35.
  21. Saffar Kohneh Quchan AH, Kordi MR, Namdari H, Shabkhiz F. Voluntary wheel running stimulates the expression of Nrf-2 and interleukin-10 but suppresses interleukin-17 in experimental autoimmune encephalomyelitis. Neuroscience Letters. 2020;738:135382.
  22. Mifflin KA, Frieser E, Benson C, Baker G, Kerr BJJJon. Voluntary wheel running differentially affects disease outcomes in male and female mice with experimental autoimmune encephalomyelitis. 2017;305:135-44.
  23. Mifflin K, Baker GB, Kerr BJJNl. Effect of voluntary wheel running on neuroactive steroid levels in murine experimental autoimmune encephalomyelitis. 2018;685:150-4.
  24. Pryor WM, Freeman KG, Larson RD, Edwards GL, White LJ. Chronic exercise confers neuroprotection in experimental autoimmune encephalomyelitis. Journal of neuroscience research. 2015;93(5):697-706.
  25. Bernardes D, Oliveira-Lima OC, da Silva TV, Faraco CCF, 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. 2013;264(1-2):24-34.
  26. Hayes K, Sprague S, Guo M, Davis W, Friedman A, Kumar A, et al. Forced, not voluntary, exercise effectively induces neuroprotection in stroke. Acta neuropathologica. 2008;115(3):289-96.
  27. Kinni H, Guo M, Ding JY, Konakondla S, Dornbos III D, Tran R, et al. Cerebral metabolism after forced or voluntary physical exercise. Brain research. 2011;1388:48-55.
  28. Zhang F, Wu Y, Jia JJN. Exercise preconditioning and brain ischemic tolerance. 2011;177:170-6.
  29. Le Page C, Ferry A, Rieu M. Effect of muscular exercise on chronic relapsing experimental autoimmune encephalomyelitis. Journal of applied physiology. 1994;77(5):2341-7.
  30. Brown DA, Johnson MS, Armstrong CJ, Lynch JM, Caruso NM, Ehlers LB, et al. Short-term treadmill running in the rat: what kind of stressor is it? Journal of applied physiology. 2007;103(6):1979-85.
  31. Klaren RE, Motl RW, Woods JA, Miller SD. Effects of exercise in experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis). Journal of neuroimmunology. 2014;274(1-2):14-9.
  32. Larochelle C, Alvarez JI, Prat AJFL. How do immune cells overcome the blood–brain barrier in multiple sclerosis? 2011;23(585):3770-80.
  33. Małkiewicz MA, Szarmach A, Sabisz A, Cubała WJ, Szurowska E, Winklewski PJJJon. Blood-brain barrier permeability and physical exercise. 2019;16(1):15.
  34. Alvarez JI, Cayrol R, Prat AJBeBA-MBoD. Disruption of central nervous system barriers in multiple sclerosis. 2011;1812(2):252-64.
  35. Williams JL, Klein RS. Blood-Brain Barrier Dysfunction during Central Nervous System Autoimmune Diseases. The Blood Brain Barrier and Inflammation: Springer; 2017. p. 175-86.
  36. Zăgrean A-M, Ianosi B, Sonea C, Opris I, Zăgrean L. Blood-Brain Barrier and Cognitive Function. The Physics of the Mind and Brain Disorders: Springer; 2017. p. 713-40.
  37. Ding Y-H, Young CN, Luan X, Li J, Rafols JA, Clark JC, et al. Exercise preconditioning ameliorates inflammatory injury in ischemic rats during reperfusion. 2005;109(3):237-46.
  38. Zoladz J, Majerczak J, Zeligowska E, Mencel J, Jaskolski A, Jaskolska A, et al. Moderate-intensity interval training increases serum brain-derived neurotrophic factor level and decreases inflammation in Parkinson’s disease patients. 2014;65(3):441-8.
  39. Zhang Q, Zhang J, Yan Y, Zhang P, Zhang W, Xia RJB, et al. Proinflammatory cytokines correlate with early exercise attenuating anxiety‐like behavior after cerebral ischemia. 2017;7(11):e00854.
  40. Li F, Pendy Jr JT, Ding JN, Peng C, Li X, Shen J, et al. Exercise rehabilitation immediately following ischemic stroke exacerbates inflammatory injury. 2017;39(6):530-7.
  • تاریخ دریافت: 02 تیر 1399
  • تاریخ بازنگری: 01 اردیبهشت 1400
  • تاریخ پذیرش: 06 اردیبهشت 1400
  • تاریخ اولین انتشار: 19 دی 1400
  • تاریخ انتشار: 01 فروردین 1401