اثر شش هفته فعالیت شنا بر سطوح پروتئین‌های مرتبط با میلین‌سازی بافت هیپوکمپ موش‌های صحرایی مدل مالتیپل اسکلروزیس

نوع مقاله : علمی - پژوهشی

نویسندگان

1 گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه شهید چمران اهواز، اهواز، ایران

2 گروه علوم پایه، دانشکدة دامپزشکی، دانشگاه شهید چمران اهواز، اهواز، ایران

چکیده

زمینه و هدف: مالتیپل اسکلروزیس (MS) بیماری مزمن التهابی، خودایمنی و چندعللی است که کیفیت زندگی مبتلایان را تا حد چشمگیری کاهش می‌دهد. از آنجا که فعالیت بدنی ممکن است دارای فواید ضدالتهابی و حفاظت از آکسون در این بیماران باشد، ازاین‌رو هدف از تحقیق حاضر بررسی تأثیر فعالیت بدنی از نوع شنا بر محتوای برخی از پروتئین‌های مؤثر در میلین‌سازی بافت هیپوکمپ موش‌های صحرایی مبتلا به بیماری MS القاشده با کوپریزون است.
مواد و روش‌ها: در این تحقیق 20 سر موش صحرایی نر نژاد ویستار با میانگین سن 12 هفته و وزن 14±230 گرم خریداری و به چهار گروه کنترل سالم، کنترل بیمار، سالم تمرین و تمرین بیمار تقسیم شدند. مدل بیماری MS با استفاده از غذای حاوی کوپریزون 5/0 درصد در تمام 12 هفته طول پروتکل تحقیق ایجاد شد. پس از تأیید القای MS از طریق آزمون روتارود، پروتکل شنا به مدت شش هفته انجام گرفت. بدین‌صورت که در هفتة اول 10 دقیقه فعالیت شنا را بدون اعمال بار انجام دادند و به‌منظور اعمال اضافه بار مدت زمان شنا در هر هفته پنج دقیقه اضافه شد. به‌منظور حفظ سازگاری‌های حاصل از فعالیت، مدت زمان فعالیت شنا در هفته‌های پنجم و ششم ثابت و 30 دقیقه در نظر گرفته شد. پس از پایان پروتکل تمرینی و انجام آزمون‌های روتارود و شاتل باکس به‌منظور بررسی حافظه و تعادل، بافت هیپوکمپ استخراج و مقادیر پروتئین‌های PLP و MBP با استفاده از روش وسترن بلات و مقدار پروتئین NGF با استفاده از روش الایزا اندازه‌گیری شد. داده‌ها به‌وسیلة آزمون آنوای یکراهه و سپس آزمون تعقیبی توکی در سطح معناداری کوچک‌تر از 05/0بررسی شد.
نتایج: نتایج آزمون‌های شاتل باکس و روتارود نشان داد که عملکرد حافظه و حفظ تعادل در گروه بیمار دچار اختلال‌شده و متعاقب یک دوره فعالیت شنا بهبود چشمگیری یافت (001/0P<). همچنین تفاوت معناداری در نتایج آزمون‌های شاتل باکس و روتارود در گروه‌های سالم تمرین و کنترل سالم مشاهده نشد (05/0P>). نتایج نشان داد که محتوای پروتئین‌های NGF، PLP و MBP در گروه کنترل بیمار به‌صورت معنا‌دار نسبت به گروه کنترل سالم کاهش یافت (05/0P<)، همچنین مقادیر این پروتئین‌ها در گروه تمرین بیمار نسبت به گروه کنترل بیمار به‌صورت شایان توجهی افزایش نشان داد (05/0P<). نتایج نشان داد که در محتوای پروتئین‌های NGF و PLP تفاوت معناداری بین گروه‌های سالم تمرین و کنترل سالم وجود دارد (05/0P<)، درحالی‌که در محتوای پروتئین MBP تفاوت معنا‌داری بین گروه‌های سالم تمرین و کنترل سالم وجود ندارد (05/0P>).
نتیجه‌گیری: بر اساس نتایج تحقیق حاضر احتمالاً می‌توان گفت که فعالیت ورزشی از نوع شنا با ایجاد سازگاری‌های مولکولی، تأثیرات ضدالتهابی و محافظت‌کنندة عصبی قابل توجهی دارد و می‌تواند به‌عنوان یک روش ایمن، غیردارویی و بدون عارضه برای بهبود علائم مبتلایان به MS در نظر گرفته شود.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

The impact of six weeks of swimming exercise on the levels of proteins associated with the myelination of hippocampal tissue in Wistar rats with multiple sclerosis

نویسندگان [English]

  • Mohammad Rami 1
  • Samaneh Rahdar 2
  • Sayed Shafa Marashi 1
  • Abdolhamid Habibi 1
1 Department of Sport Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
2 Department of Basic Sciences, Histology Section, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
چکیده [English]

Background and Purpose: Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and multi-factorial disease that substantially reduces patients’ quality of life. Since physical activity may offer anti-inflammatory and axonal protection benefits to these patients, this study aimed to explore the impact of swimming training on the proteins critical for the myelination of hippocampal tissue in cuprizone-induced rat’s model of MS.
Materials and Methods: In the current investigation, 20 male Wistar rats with an average age of 12 weeks and the weight of 230 g were purchased and divided randomly into four groups: healthy control, MS control, healthy training, and MS training. The MS disease model was induced by administering food containing 0.5% cuprizone for 12 weeks. Upon confirming MS induction through the rotarod test, rats underwent a six-week swimming protocol. In the first week, they performed 10 min swimming without applying loads, and thereafter the duration of swimming was added by 5 min every week. In order to maintain the adaptations the duration of the swimming for the fifth and sixth weeks was constant and was kept at 30 min. At the end of the training protocol, memory and balance were assessed via shuttle box and rotarod tests. Subsequently, the hippocampal tissue was extracted, and analyzed for determining the proteolipid protein (PLP) and Myelin basic protein (MBP) protein levels by using western blot and the amount of Nerve growth factor (NGF) protein was measured by using the ELISA method. The data were analyzed using one-way ANOVA and post-hoc comparisons were made by using Tukey's test at a significance level of p<0.05.
Results: The findings of the shuttle box and rotarod tests revealed that the MS group had impaired memory function and balance maintenance, but these improved significantly after swimming training (p<0.001). No significant difference was observed in the results of the shuttle box and rotarod tests between healthy training and healthy control groups (p>0.05). The results of the present study showed that NGF, PLP and MBP proteins in the patient control group were significantly lower compared to the healthy control group (p<0.05). Furthermore, data analyses showed that the amounts of these proteins increased significantly in the MS training group compared to the MS control group (p<0.05). The results showed that there was a significant difference for NGF and PLP proteins between healthy training group and healthy control group (p<0.05), whereas, no significant differences in MBP protein levels were found between the healthy training and healthy control groups (p>0.05).
Conclusion: Based on the current research findings, it can be concluded that swimming exercise has notable anti-inflammatory and neuroprotective effects through favourable molecular adaptations, and it can probably be considered as a safe, non-pharmacological and complication-free method to improve the symptoms in MS patients.

کلیدواژه‌ها [English]

  • Swimming exercise
  • Multiple Sclerosis
  • Inflammatory disease
  • Molecular adaptation
  • Myelination

مراجع

  1. Maciak K, Dziedzic A, Saluk J. Remyelination in multiple sclerosis from the miRNA perspective. Front. Mol. Neurosci. 2023 Jun 1;16:1199313.
  2. Martinsen V, Kursula P. Multiple sclerosis and myelin basic protein: insights into protein disorder and disease. Amino Acids. 2022;54(1):99-109.
  3. Calahorra L, Camacho-Toledano C, Serrano-Regal MP, Ortega MC, Clemente D. Regulatory cells in multiple sclerosis: From blood to brain. Biomedicines. 2022 Feb 1;10(2):335.
  4. Lorenzini L, Baldassarro VA, Stanzani A, Giardino L. Nerve Growth Factor: The First Molecule of the Neurotrophin Family. Adv. Exp. Med. Biol. 2021;1331:3-10.
  5. Guarnieri G, Sarchielli E, Comeglio P, Herrera-Puerta E, Piaceri I, Nacmias B, et al. Tumor Necrosis Factor α Influences Phenotypic Plasticity and Promotes Epigenetic Changes in Human Basal Forebrain Cholinergic Neuroblasts. Int. J. Mol. Sci. 2020;21(17):6128.
  6. Tonev D, Momchilova A. Therapeutic Plasma Exchange and Multiple Sclerosis Dysregulations: Focus on the Removal of Pathogenic Circulatory Factors and Altering Nerve Growth Factor and Sphingosine-1-Phosphate Plasma Levels. Current issues in molecular biology(CIMB). 2023;45(10):7749-74.
  7. Terracina S, Ferraguti G, Tarani L, Fanfarillo F, Tirassa P, Ralli M, et al. Nerve Growth Factor and Autoimmune Diseases. Current issues in molecular biology(CIMB). 2023;45(11):8950-73.
  8. Acosta CM, Cortes C, MacPhee H, Namaka MP. Exploring the role of nerve growth factor in multiple sclerosis: implications in myelin repair. CNS Neurol Disord Drug Targets. 2013;12(8):1242-56.
  9. Plemel JR, Liu WQ, Yong VW. Remyelination therapies: a new direction and challenge in multiple sclerosis. Nat. Rev. Drug Discov. 2017;16(9):617-34.
  10. Kister A, Kister I. Overview of myelin, major myelin lipids, and myelin-associated proteins. Front. Chem. 2023; 21;10:1041961.
  11. Smirnova EV, Rakitina TV, Ziganshin RH, Arapidi GP, Saratov GA, Kudriaeva AA, Belogurov AA. Comprehensive Atlas of the Myelin Basic Protein Interaction Landscape. Biomolecules. 2021;11(11):1628.
  12. Greer JM, Trifilieff E, Pender MP. Correlation between anti-myelin proteolipid protein (PLP) antibodies and disease severity in multiple sclerosis patients with PLP response-permissive HLA types. Front. immunol. 2020; 21;11:1891.
  13. Guo LY, Lozinski B, Yong VW. Exercise in multiple sclerosis and its models: Focus on the central nervous system outcomes. J. Neurosci. Res. 2020;98(3):509-23.
  14. Campbell E, Coulter EH, Paul L. High intensity interval training for people with multiple sclerosis: A systematic review. Mult. Scler. Relat. Disord. 2018;24:55-63.
  15. Joisten N, Proschinger S, Rademacher A, Schenk A, Bloch W, Warnke C, et al. High-intensity interval training reduces neutrophil-to-lymphocyte ratio in persons with multiple sclerosis during inpatient rehabilitation. Mult. Scler. Int. 2021;27(7):1136-9.
  16. Taul-Madsen L, Connolly L, Dennett R, Freeman J, Dalgas U, Hvid LG. Is aerobic or resistance training the most effective exercise modality for improving lower extremity physical function and perceived fatigue in people with multiple sclerosis? A systematic review and meta-analysis. Arch Phys Med Rehabil. 2021; 1;102(10):2032-48.
  17. Langeskov-Christensen M, Hvid LG, Jensen HB, Nielsen HH, Petersen T, Stenager E, Dalgas U. Efficacy of high-intensity aerobic exercise on common multiple sclerosis symptoms. Acta Neurol. Scand.. 2022;145(2):229-38.
  18. Torres-Costoso A, Martínez-Vizcaíno V, Reina-Gutiérrez S, Álvarez-Bueno C, Guzmán-Pavón MJ, Pozuelo-Carrascosa DP, et al. Effect of Exercise on Fatigue in Multiple Sclerosis: A Network Meta-analysis Comparing Different Types of Exercise. Arch Phys Med Rehabil. 2022;103(5):970-87.e18.
  19. 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.
  20. Deforges S, Branchu J, Biondi O, Grondard C, Pariset C, Lécolle S, et al. Motoneuron survival is promoted by specific exercise in a mouse model of amyotrophic lateral sclerosis. Physiol. J. 2009;587(Pt 14):3561-72.
  21. Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol. 2008;7(12):1139-51.
  22. Ohgomori T, Jinno S. Cuprizone-induced demyelination in the mouse hippocampus is alleviated by phytoestrogen genistein. Toxicol. Appl. Pharmacol. 2019;363:98-110.
  23. Liu C, Zhang N, Zhang R, Jin L, Petridis AK, Loers G, et al. Cuprizone-Induced Demyelination in Mouse Hippocampus Is Alleviated by Ketogenic Diet. J. Agric. Food Chem. 2020;68(40):11215-28.
  24. Kim W, Hahn KR, Jung HY, Kwon HJ, Nam SM, Kim JW, et al. Melatonin ameliorates cuprizone-induced reduction of hippocampal neurogenesis, brain-derived neurotrophic factor, and phosphorylation of cyclic AMP response element-binding protein in the mouse dentate gyrus. Brain Behav. 2019;9(9):e01388.
  25. Papadopoulos D, Dukes S, Patel R, Nicholas R, Vora A, Reynolds R. Substantial archaeocortical atrophy and neuronal loss in multiple sclerosis. Brain Pathol. 2009;19(2):238-53.
  26. Klein B, Mrowetz H, Barker CM, Lange S, Rivera FJ, Aigner L. Age influences microglial activation after cuprizone-induced demyelination. Front. aging neurosci. 2018 Sep 20;10:278.
  27. Rocca MA, Barkhof F, De Luca J, Frisén J, Geurts JJG, Hulst HE, et al. The hippocampus in multiple sclerosis. Lancet Neurol. 2018;17(10):918-26.
  28. Zimmermann J, Emrich M, Krauthausen M, Saxe S, Nitsch L, Heneka MT, et al. IL-17A Promotes Granulocyte Infiltration, Myelin Loss, Microglia Activation, and Behavioral Deficits During Cuprizone-Induced Demyelination. Mol Neurobiol. 2018;55(2):946-57.
  29. Ye JN, Chen XS, Su L, Liu YL, Cai QY, Zhan XL, et al. Progesterone alleviates neural behavioral deficits and demyelination with reduced degeneration of oligodendroglial cells in cuprizone-induced mice. PLoS One. 2013;8(1):e54590.
  30. Ghotbeddin Z, Basir Z, Jamshidian J, Delfi F. Modulation of behavioral responses and CA1 neuronal death by nitric oxide in the neonatal rat's hypoxia model. Brain Behav. 2020;10(11):e01841.
  31. Ghotbeddin Z, Khazaeel K, Tabandeh MR, Aliheydari M, Yaghoubi H. Effects of omega-3 fatty acid supplementation during chronic maternal hypoxia on behavioral disorders in male rat offspring: The role of Trk family and oxidative stress. Metab. Brain Dis. 2022;37(6):1959-67.
  32. Lubrich C, Giesler P, Kipp M. Motor behavioral deficits in the cuprizone model: Validity of the rotarod test paradigm. Int. J. Mol. Sci. 2022;23(19):11342.
  33. Zarrindast MR, Farajzadeh Z, Rostami P, Rezayof A, Nourjah P. Involvement of the ventral tegmental area (VTA) in morphine-induced memory retention in morphine-sensitized rats. Behav. Brain Res. 2005;163(1):100-6.
  34. Kim JY, Yi ES, Lee H, Kim JS, Jee YS, Kim SE, et al. Swimming Exercise Ameliorates Symptoms of MOG-Induced Experimental Autoimmune Encephalomyelitis by Inhibiting Inflammation and Demyelination in Rats. Int. Neurourol. J. 2020;24(Suppl 1):S39-47.
  35. Haase S, Linker RA. Inflammation in multiple sclerosis. Ther. Adv. Neurol. Disord. 2021 Apr;14:17562864211007687.
  36. Mandolesi G, Bullitta S, Fresegna D, De Vito F, Rizzo FR, Musella A, Guadalupi L, Vanni V, Bassi MS, Buttari F, Viscomi MT. Voluntary running wheel attenuates motor deterioration and brain damage in cuprizone-induced demyelination. Neurobiol. Dis. 2019 Sep 1;129:102-17.
  37. Naghibzadeh M, Ranjbar R, Tabandeh MR, Habibi A. Effects of Two Training Programs on Transcriptional Levels of Neurotrophins and Glial Cells Population in Hippocampus of Experimental Multiple Sclerosis. Int J Sports Med. 2018;39(08):604-12.
  38. 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.
  39. Kim T-W, Sung Y-H. Regular exercise promotes memory function and enhances hippocampal neuroplasticity in experimental autoimmune encephalomyelitis mice. Neurosci. 2017;346:173-81.
  40. Kim TW, Sung YH. Regular exercise promotes memory function and enhances hippocampal neuroplasticity in experimental autoimmune encephalomyelitis mice. Neurosci. 2017;346:173-81.
  41. Gold SM, Schulz KH, Hartmann S, Mladek M, Lang UE, Hellweg R, et al. Basal serum levels and reactivity of nerve growth factor and brain-derived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls. J. Neuroimmunol. 2003;138(1-2):99-105.
  42. Schulz KH, Gold SM, Witte J, Bartsch K, Lang UE, Hellweg R, et al. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J. Neurol. Sci. 2004;225(1-2):11-8.
  43. Xie Y, Wu Z, Zhou L, Sun L, Xiao L, Wang G. Swimming Exercise Modulates Gut Microbiota in CUMS-Induced Depressed Mice. Neuropsychiatr Dis Treat. 2022;18:749-60.
  44. Wigati KW, Bintari MP, Rejeki PS, Wungu CD, Pranoto A, Ramadhan RN, Setiawan HK, Munir M, Halim S. The effect of 4 week-long swimming exercise intervention on increased serotonin levels in male mice (Mus musculus). Comp. Exerc. Physiol. 2023; 4;1(aop):1-0.
  45. van Galen KA, Ter Horst KW, Serlie MJ. Serotonin, food intake, and obesity. Obes Rev. 2021;22(7):e13210.
  46. Waubant E, Lucas R, Mowry E, Graves J, Olsson T, Alfredsson L, Langer-Gould A. Environmental and genetic risk factors for MS: an integrated review. Ann Clin Transl Neurol. 2019;6(9):1905-22.
  47. Park HS, Kim TW, Park SS, Lee SJ. Swimming exercise ameliorates mood disorder and memory impairment by enhancing neurogenesis, serotonin expression, and inhibiting apoptosis in social isolation rats during adolescence. J Exerc Rehabil. 2020;16(2):132-40.

فایل ها

سابقه مقاله

  • تاریخ دریافت: 01 بهمن 1402
  • تاریخ بازنگری: 01 اسفند 1402
  • تاریخ پذیرش: 26 اسفند 1402
  • تاریخ اولین انتشار: 13 فروردین 1403
  • تاریخ انتشار: 01 اردیبهشت 1403

هم رسانی

ارجاع به این مقاله

آمار