The Effects of Voluntary Swimming on iNOS and COX-2 Protein Contents as Well as Memory and Motor Performance in Cuprizone-Induced Multiple Sclerosis Rats Model

Document Type : Original Article(s)

Authors

1 MSc, Department of Sport Physiology, School of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

2 Assistant Professor, Department of Sport Physiology, School of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

3 Professor, Department of Sport Physiology, School of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

4 Assistant Professor, Health Through Exercise and Active Living (HEAL) Research Unit, Department of Biomedical Sciences, School of Medicine and Health Sciences, University Malaysia Sabah, Kota Kinabalu 88400, Jalan UMS, Kota Kinabalu 88450, Sabah, Malaysia

Abstract

Background: Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system and is mediated by the immune system. Since physical activity has anti-inflammatory and anti-oxidative effects, Therefore, this study aims to investigate the effect of voluntary swimming activity on the iNOS & COX-2 protein content, as well as the cognitive and motor performance of the Multiple Sclerosis rats model.
Methods: In the present study, 20 rats with an average age of 12 weeks were categorized into four groups, including healthy control, MS control, healthy training, and MS training. To induce MS, the rats of the MS groups were fed food infused with 0.5%cuprizone throughout the entire 12-week research protocol. After the end of 6 weeks of training protocol and conducting behavioral tests, the hippocampus tissue was extracted, and the number of proteins was measured using the western blot method.
Findings: The results of the memory and motor function tests revealed that subjects with MS had impaired memory function, motor activity, and difficulty maintaining balance. However, following a period of swimming activity, these functions significantly improved. The results also showed that the levels of iNOS and COX-2 proteins in the MS control group were significantly elevated compared to the healthy control group. On the other hand, the MS training group showed significant reductions in the levels of these proteins compared to the MS control group.
Conclusion: Based on the results of the current research, voluntary swimming exercise activity could potentially lead to more nerve protection and improvement of memory function, motor activity, and balance in patients with MS and can be promising as a non-pharmacological treatment strategy.

Highlights

Sayed Shafa Marashi:  Google Scholar 

Mohammad Ram: PubMed, Google Scholar 

Saeed Shakeryan: PubMed, Google Scholar 

Maryama Awang Daud: PubMed , Google Scholar 

Keywords

Main Subjects

References

  1. Calahorra L, Camacho-Toledano C, Serrano-Regal MP, Ortega MC, Clemente D. Regulatory cells in multiple sclerosis: From blood to brain. Biomedicines 2022; 10(2): 335.
  2. Disanto G, Zecca C, MacLachlan S, Sacco R, Handunnetthi L, Meier UC, et al. Prodromal symptoms of multiple sclerosis in primary care. Ann Neurol 2018; 83(6): 1162-73.
  3. Förster M, Nelke C, Räuber S, Lassmann H, Ruck T, Sormani MP, et al. Nitrosative Stress Molecules in Multiple Sclerosis: A Meta-Analysis. Biomedicines 2021; 9(12): 1899.
  4. Khaledi E, Noori T, Mohammadi-Farani A, Sureda A, Dehpour AR, Yousefi-Manesh H, et al. Trifluoperazine reduces cuprizone-induced demyelination via targeting Nrf2 and IKB in mice. Eur J Pharmacol 2021; 909: 174432.
  5. Shefa U, Yeo SG, Kim MS, Song IO, Jung J, Jeong NY, et al. Role of gasotransmitters in oxidative stresses, neuroinflammation, and neuronal repair. Biomed Res Int 2017; 2017: 1689341.
  6. Kamble M, Saadi F, Kumar S, Saha B, Sarma JD. Inducible Nitric Oxide Synthase deficiency leads to early demyelination by altering the balance between pro-and anti-inflammatory responses against Murine-β-Coronavirus. bioRxiv 2022: 2022.02. 08.479662.
  7. Kumar N, Gupta G, Anilkumar K, Fatima N, Karnati R, Reddy GV, et al. Lipoxygenase metabolites of α-linolenic acid, [13-(S)-HPOTrE and 13-(S)-HOTrE], mediate anti-inflammatory effects by inactivating NLRP3 inflammasome. Sci Rep 2016; 6(1): 31649.
  8. Ferrer MD, Busquets-Cortés C, Capó X, Tejada S, Tur JA, Pons A, et al. Cyclooxygenase-2 inhibitors as a therapeutic target in inflammatory diseases. Curr Med Chem 2019; 26(18): 3225-41.
  9. Tang X, Li Z, Zhang W, Yao Z. Nitric oxide might be an inducing factor in cognitive impairment in Alzheimer's disease via downregulating the monocarboxylate transporter 1. Nitric Oxide 2019; 91: 35-41.
  10. Nakamura T, Cho DH, Lipton SA. Redox regulation
    of protein misfolding, mitochondrial dysfunction, synaptic damage, and cell death in neurodegenerative diseases. Exp Neurol 2012; 238(1): 12-21.
  11. Lan M, Tang X, Zhang J, Yao Z. Insights in pathogenesis of multiple sclerosis: nitric oxide may induce mitochondrial dysfunction of oligodendrocytes. Rev Neurosci 2018; 29(1): 39-53.
  12. Ghasemi M, Fatemi A. Pathologic role of glial nitric oxide in adult and pediatric neuroinflammatory diseases. Neurosci Biobehav Rev 2014; 45: 168-82.
  13. Rose JW, Hill KE, Watt HE, Carlson NG. Inflammatory cell expression of cyclooxygenase-2 in the multiple sclerosis lesion. J Neuroimmunol 2004; 149(1-2): 40-9.
  14. Metsios GS, Moe RH, Kitas GD. Exercise and inflammation. Best Pract Res Clin Rheumatol 2020; 34(2): 101504.
  15. Lin JY, Kuo WW, Baskaran R, Kuo CH, Chen YA, Chen WS, et al. Swimming exercise stimulates IGF1/PI3K/Akt and AMPK/SIRT1/PGC1α survival signaling to suppress apoptosis and inflammation in aging hippocampus. Aging (Albany NY) 2020; 12(8): 6852-64.
  16. Kim TW, Park SS, Shin MS, Park HS, Baek SS. Treadmill exercise ameliorates social isolation-induced memory impairment by enhancing silent information regulator-1 expression in rats. J Exerc Rehabil 2020; 16(3): 227-33.
  17. 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.
  18. 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; 102(10): 2032-48.
  19. Langeskov-Christensen M, Hvid LG, Jensen HB, Nielsen HH, Petersen T, Stenager E, et al. Efficacy of high-intensity aerobic exercise on common multiple sclerosis symptoms. Acta Neurol. Acta Neurol Scand 2022; 145(2): 229-38.
  20. 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.
  21. Mahalakshmi B, Maurya N, Lee SD, Kumar VB. Possible neuroprotective mechanisms of physical exercise in neurodegeneration. Int J Mol Sci 2020; 21(16): 5895.
  22. 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. J Physiol 2009; 587(Pt 14): 3561-72.
  23. 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.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. Hagemeier K, Lürbke A, Hucke S, Albrecht S, Preisner A, Klassen E, et al. Puma, but not noxa is essential for oligodendroglial cell death. Glia 2013; 61(10): 1712-23.
  30. McQualter JL, Bernard CC. Multiple sclerosis: a battle between destruction and repair. J Neurochem
    2007; 100(2): 295-306.
  31. Hashemi R, Morshedi M, Asghari Jafarabadi M, Altafi D, Saeed Hosseini-Asl S, Rafie-Arefhosseini S. Anti-inflammatory effects of dietary vitamin D(3) in patients with multiple sclerosis. Neurol Genet 2018; 4(6): e278.
  32. Ünsal C, Özcan M. Neurotoxicity of cuprizone in female and male rats: Electrophysiological observations. Neurophysiol 2018; 50: 108-15.
  33. Omotoso GO, Gbadamosi IT, Afolabi TT, Abdulwahab AB, Akinlolu AA. Ameliorative effects of Moringa on cuprizone-induced memory decline in rat model of multiple sclerosis. Anat Cell Biol 2018; 51(2): 119-27.
  34. Tomas-Roig J, Torrente M, Cabré M, Vilella E, Colomina MT. Long lasting behavioural effects on cuprizone fed mice after neurotoxicant withdrawal. Behav Brain Res 2019; 363: 38-44.
  35. Han SR, Kang YH, Jeon H, Lee S, Park SJ, Song DY, et al. Differential expression of miRNAs and behavioral change in the cuprizone-induced demyelination mouse model. Int J Mol Sci 2020; 21(2): 646.
  36. 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). Exp Neurol 2015; 271: 279-90.
  37. Donia SA, Allison DJ, Gammage KL, Ditor DS. The effects of acute aerobic exercise on mood and inflammation in individuals with multiple sclerosis and incomplete spinal cord injury. NeuroRehabilitation 2019; 45(1): 117-24.
  38. 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.
  39. 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.
  40. 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 J 2021; 27(7): 1136-9.
  41. Song SH, Jee YS, Ko IG, Lee SW, Sim YJ, Kim DY, et al. Treadmill exercise and wheel exercise improve motor function by suppressing apoptotic neuronal cell death in brain inflammation rats. J Exerc Rehabil 2018; 14(6): 911-9.
  42. Tintore M, Vidal-Jordana A, Sastre-Garriga J. Treatment of multiple sclerosis - success from bench to bedside. Nat Rev Neurol 2019; 15(1): 53-8.
Journal of Isfahan Medical School
Volume 41, Issue 748
4th Week, February
January and February 2024
Pages 1118-1127

Files

Share

How to cite

Statistics