نوع مقاله : مقاله پژوهشی Released under CC BY-NC 4.0 license I Open Access I
نویسندگان
1 دانشجوی دکتری فیزیولوژی ورزش، گروه علوم ورزشی، دانشکده علوم انسانی، دانشگاه تربیت مدرس، تهران، ایران،
2 دانشیار گروه علوم ورزشی، دانشکده علوم انسانی، دانشگاه تربیت مدرس، تهران، ایران
3 استاد گروه علوم ورزشی، دانشکده علوم انسانی، دانشگاه تربیت مدرس، تهران، ایران،
4 استادگروه فیزیولوژی ورزشی، دانشکده علوم ورزشی و تندرستی، دانشگاه تهران، تهران، ایران،
چکیده
مقدمه: مالتیپل اسکلروزیس (MS) یک بیماری التهابی خودایمنی است که بر عملکرد شناختی در طول توسعۀ بیماری اثر دارد. یکی از تغییرات مهم در سیستم اعصاب مرکزی این بیماران اختلال سیناپسی است که پیش از دمیلینه شدن اکسونها و مسیرهای عصبی رخ میدهد. پژوهشهای پیشین نشاندهندۀ این نکته است که فعالیت بدنی در پیشگیری و درمان چنین شرایطی امیدوارکننده است. تحقیق حاضر با هدف بررسی تغییرات حاصل از ورزش شنا بر پروتئین سیناپتوزومی SNAP25 بافت مغز دخیل در اختلالات شناختی و التهابی MS انجام شد.
روش پژوهش: از 21 موش سوری C57BL/6 در سه گروه به تعداد مساوی کنترل، آنسفالومیلیت خودایمنی تجربی بدون تمرین و با چهار هفته شنای هوازی استفاده شد. نمرات بالینی روزانه و سطح پروتئین SNAP25 پس از چهار هفته تمرین با روش وسترن بلات اندازهگیری شد.
یافتهها: القای EAE سطح SNAP25 را نسبت به گروه کنترل سالم افزایش داد، اما ورزش شنا توانست آن را .۲۷ درصد کاهش دهد نمرات بالینی نیز در پی انجام ورزش در موشهای بیمار بهبود یافت.
نتیجهگیری: ورزش منظم روزانه با تنظیم بیان SNAP25 در بافت مغز، احتمالاً رهایش واسطههای عصبی و عوامل تروفیک در ناحیۀ سیناپس را در شرایط التهابی تعدیل میکند و موجب بهبود علائم اختلال شناختی میشود.
کلیدواژهها
موضوعات
عنوان مقاله [English]
The Effect of Aerobic Swimming on Synaptic Protein Expression and Improvement of Cognitive Function in Multiple Sclerosis Mice Model
نویسندگان [English]
- Soheila Banasadegh 1
- Shahnaz Shahrbanian 2
- Reza Ghara khanlou 3
- Mohammadreza Kordi 4
1 Department of Sport Sciences, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran
2 Department of Sport Sciences, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran
3 Department of Sport Sciences, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran
4 Department of Sports Physiology, Faculty of Health and Sports Sciences, University of Tehran, Tehran, Iran.
چکیده [English]
Introduction: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the CNS that impairs cognitive function during its progression. A notable alteration in the CNS of these patients is synaptic dysfunction, which precedes axonal and neural pathway demyelination. Previous research shows that physical activity is promising potential in the prevention and management of these conditions. This study aimed to examine the effects of swimming exercise on the levels of the presynaptic membrane protein SNAP25 in the brain tissue of female mice experiencing cognitive and inflammatory disorders, using the experimental autoimmune encephalomyelitis (EAE) animal model.
Methods: A total of 21 C57BL/6 mice were divided into 3 groups with equal numbers: control, EAE without exercise, and EAE with aerobic swimming exercise. Clinical scores were recorded daily, and SNAP25 protein levels were measured by Western blot method after the 4-week exercise period.
Results: The induction of EAE increased SNAP25 levels compared to the healthy control group, but swimming exercise reduced these levels by 27% (P-value=0.0003, F=42.92, EF=0.85). Additionally, clinical scores improved in the exercised mice with the disease.
Conclusion: Aerobic swimming for four weeks by regulating the expression of SNAP25 in the brain tissue and modulating the release of neural mediators and nutritional factors in the synaptic area improves the symptoms of mild cognitive impairment and clinical symptoms in mice model of MS.
Methods: A total of 21 C57BL/6 mice were divided into 3 groups with equal numbers: control, EAE without exercise, and EAE with aerobic swimming exercise. Clinical scores were recorded daily, and SNAP25 protein levels were measured by Western blot method after the 4-week exercise period.
Results: The induction of EAE increased SNAP25 levels compared to the healthy control group, but swimming exercise reduced these levels by 27% (P-value=0.0003, F=42.92, EF=0.85). Additionally, clinical scores improved in the exercised mice with the disease.
Conclusion: Aerobic swimming for four weeks by regulating the expression of SNAP25 in the brain tissue and modulating the release of neural mediators and nutritional factors in the synaptic area improves the symptoms of mild cognitive impairment and clinical symptoms in mice model of MS.
کلیدواژهها [English]
- EAE Induction
- Synaptic Destruction
- SNAP25
- Mild Cognitive Impairment
- Aerobic Exercise
- Faissner S, Gold R. Progressive multiple sclerosis: latest therapeutic developments and future directions. Ther Adv Neurol Disord. 2019;905-922. 10.1038/s41573-019-0035-2. https://pubmed.ncbi.nlm.nih.gov/31598138/
- Gilmour H, Ramage-Morin PL, Wong SL. Multiple sclerosis: Prevalence and impact. Health Rep. 2018;29(1):3-8. PMID: 29341025. https://pubmed.ncbi.nlm.nih.gov/29341025/
- Schwarz K, Schmitz F. Synapse dysfunctions in multiple sclerosis. International Journal of Molecular Sciences. 2023;24(2):1639. 10.3390/ijms24021639. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9862173/
- Javadi AHS, Shafikhani AA, Beizapour N. Evaluation of the determinants of cognitive dysfunction in patients with multiple sclerosis. Middle East Current Psychiatry. 2022;29(1):1-7. 10.1186/s43045-022-00262-5. https://mecp.springeropen.com/articles/10.1186/s43045-022-00262-5
- Bebo B, Cintina I, LaRocca N, Ritter L, Talente B, Hartung D, et al. The economic burden of multiple sclerosis in the United States: estimate of direct and indirect costs. Neurology. 2022;98(18):e1810-e7. 10.1212/WNL.0000000000200150. https://pubmed.ncbi.nlm.nih.gov/35418457/
- Etemadifar M, Ghourchian S, Sabeti F, Akbari M, Etemadifar F, Salari M. The higher prevalence of multiple sclerosis among Iranian Georgians; new clues to the role of genetic factors. Revue Neurologique. 2020;176(1-2):113-7. 10.1016/j.neurol.2019.04.004. https://pubmed.ncbi.nlm.nih.gov/31182312/
- Bellingacci L, Mancini A, Gaetani L, Tozzi A, Parnetti L, Di Filippo M. Synaptic dysfunction in multiple sclerosis: a red thread from inflammation to network disconnection. International Journal of Molecular Sciences. 2021;22(18):9753. 10.3390/ijms22189753. https://pubmed.ncbi.nlm.nih.gov/34575917/
- Nakhzari Khodakheir J, Haghighi A, Hamedinia MR, Ahmadi A. The effects of combined exercise training with aerobic dominant and coenzyme Q10 supplementation on muscular function in patient with multiple sclerosis. Internal Medicine Today. 2018;24(4):286-93. http://imtj.gmu.ac.ir/article-1-2974-en.html http://jams.arakmu.ac.ir/browse.php?a_id=5633&sid=1&slc_lang=en
- Achiron A, Polliack M, Rao S, Barak Y, Lavie M, Appelboim N, et al. Cognitive patterns and progression in multiple sclerosis: construction and validation of percentile curves. Journal of neurology, neurosurgery, and psychiatry. 2005;76(5):744. 10.1136/jnnp.2004.045518. https://pubmed.ncbi.nlm.nih.gov/15834042/
- Öhrfelt A, Brinkmalm A, Dumurgier J, Zetterberg H, Bouaziz-Amar E, Hugon J, et al. A novel ELISA for the measurement of cerebrospinal fluid SNAP-25 in patients with Alzheimer’s disease. Neuroscience. 2019;420:136-44. 10.1016/j.neuroscience.2018.11.038. https://pubmed.ncbi.nlm.nih.gov/30528858/
- Motl RW, Gosney J. Effect of exercise training on quality of life in multiple sclerosis: a meta-analysis. Multiple Sclerosis Journal. 2008;14(1):129-35. 10.1177/1352458507080464. https://pubmed.ncbi.nlm.nih.gov/17881388/
- Motl RW, McAuley E, Snook EM. Physical activity and multiple sclerosis: a meta-analysis. Multiple Sclerosis Journal. 2005;11(4):459-63. https://doi.org/10.1191/1352458505ms1188oa. https://pubmed.ncbi.nlm.nih.gov/16042230/
- Motl RW, Pilutti LA. Is physical exercise a multiple sclerosis disease modifying treatment? Expert review of neurotherapeutics. 2016;16(8):951-60. 10.1080/14737175.2016.1193008. https://pubmed.ncbi.nlm.nih.gov/27219279/
- Motl RW, Sandroff BM, Kwakkel G, Dalgas U, Feinstein A, Heesen C, et al. Exercise in patients with multiple sclerosis. The lancet neurology. 2017;16(10):848-56. 10.1016/S1474-4422(17)30281-8. https://pubmed.ncbi.nlm.nih.gov/28920890/
- Pilutti LA, Platta ME, Motl RW, Latimer-Cheung AE. The safety of exercise training in multiple sclerosis: a systematic review. Journal of the neurological sciences. 2014;343(1-2):3-7. 10.1016/j.jns.2014.05.016. https://pubmed.ncbi.nlm.nih.gov/24880538/
- Pinho RA, Aguiar Jr AS, Radák Z. Effects of resistance exercise on cerebral redox regulation and cognition: an interplay between muscle and brain. Antioxidants. 2019;8(11):529. 10.3390/antiox8110529. https://pubmed.ncbi.nlm.nih.gov/31698763/
- Correale L, Buzzachera CF, Liberali G, Codrons E, Mallucci G, Vandoni M, et al. Effects of combined endurance and resistance training in women with multiple sclerosis: a randomized controlled study. Frontiers in Neurology. 2021;12:698460. 10.3389/fneur.2021.698460. https://pubmed.ncbi.nlm.nih.gov/34421801/
- 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. 10.1177/1756285611430719. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302199/
- Shahidi SH, Kordi MR, Rajabi H, Malm C, Shah F, Quchan ASK. Exercise modulates the levels of growth inhibitor genes before and after multiple sclerosis. Journal of neuroimmunology. 2020;341:577172. 10.1016/j.jneuroim.2020.577172. https://pubmed.ncbi.nlm.nih.gov/32028123/
- Emadi S, Hemati Farsani Z, Dehestani Ardakani M. Effects of preconditioning or following exercise on brain-derived neurotrophic factor (BDNF): A systematic review in animal models of multiple sclerosis. Journal of Exercise & Organ Cross Talk. 2023;3(1):43-52. 10.22034/JEOCT.2023.379278.1062. https://www.jeoct.com/article_168876.html
- Just-Borràs L, Cilleros-Mañé V, Hurtado E, Biondi O, Charbonnier F, Tomàs M, et al. Running and swimming differently adapt the BDNF/TrkB pathway to a slow molecular pattern at the NMJ. International Journal of Molecular Sciences. 2021;22(9):4577. 10.3390/ijms22094577. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123836/
- Nikukheslat SD, Karimi P, Sadri I. Effect of Aerobic Training on Synaptic Integrity Proteins in Hippocampus and Prefrontal Cortex of Type II Diabetic Rats. Medical Journal of Tabriz University of Medical Sciences. 2020;42(2):160-7. 10.34172/mj.2020.032. https://mj.tbzmed.ac.ir/Article/27138
- Segal JP, Bannerman CA, Silva JR, Haird CM, Baharnoori M, Gilron I, et al. Chronic mechanical hypersensitivity in experimental autoimmune encephalomyelitis is regulated by disease severity and neuroinflammation. Brain, behavior, and immunity. 2020;89:314-25. 10.1016/j.bbi.2020.07.010. https://pubmed.ncbi.nlm.nih.gov/32688029/
- Zeraati M, Najdi N, Mosaferi B, Salari A-A. Environmental enrichment alters neurobehavioral development following maternal immune activation in mice offspring with epilepsy. Behavioural brain research. 2021;399:112998. 10.1016/j.bbr.2020.112998. https://pubmed.ncbi.nlm.nih.gov/33197458/
- Just-Borràs L, Hurtado E, Cilleros-Mañé V, Biondi O, Charbonnier F, Tomàs M, et al. Running and swimming prevent the deregulation of the BDNF/TrkB neurotrophic signalling at the neuromuscular junction in mice with amyotrophic lateral sclerosis. Cellular and Molecular Life Sciences. 2020;77(15):3027-40. 10.1007/s00018-019-03337-5. https://pubmed.ncbi.nlm.nih.gov/31646358/
- Na J, Lee E, Im SI, Kim Y-j, Kim SY, Kim BJ. Exercise training improves adipocyte accumulation and muscle fibrosis by TGF-β1 and α-SMA reduction after botulinum toxin type A administration in mice. 2020. https://doi.org/10.21203/rs.3.rs-17126/v1. https://europepmc.org/article/ppr/ppr122938
- Ochneva A, Zorkina Y, Abramova O, Pavlova O, Ushakova V, Morozova A, et al. Protein Misfolding and aggregation in the brain: Common Pathogenetic pathways in neurodegenerative and mental disorders. International Journal of Molecular Sciences. 2022;23(22):14498. 10.3390/ijms232214498. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695177/
- Kivisäkk P, Carlyle BC, Sweeney T, Quinn JP, Ramirez CE, Trombetta BA, et al. Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer’s disease. Alzheimer's Research & Therapy. 2022;14(1):1-11. 10.1186/s13195-022-01002-x. https://pubmed.ncbi.nlm.nih.gov/35461266/
- Zhang H, Therriault J, Kang MS, Ng KP, Pascoal TA, Rosa-Neto P, et al. Cerebrospinal fluid synaptosomal-associated protein 25 is a key player in synaptic degeneration in mild cognitive impairment and Alzheimer’s disease. Alzheimer's research & therapy. 2018;10:1-11. 10.1186/s13195-018-0407-6. https://pubmed.ncbi.nlm.nih.gov/30115118/