Journal of Paramedical Sciences & Rehabilitation

Journal of Paramedical Sciences & Rehabilitation

The effect of eight weeks of neuromuscular training on serum levels of OPA1 and Atrogin-1 in patients with multiple sclerosis

Document Type : Original Article

Authors
Ahmad Shahid Razi 1
Khosro Jalali Dehkordi 1
Asaad Adnan Aziz 2
Farzaneh Taghian 1
Ahmad Chitsaz 3
1 Department of Sports Physiology, Faculty of Sports Sciences, Isf.C., Islamic Azad University, Isfahan, Iran
2 College of Physical Education and Sports Science, University of Al-Qadisiyah, Iraq
3 Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
10.22038/jpsr.2026.95178.2781
Abstract
Purpose:
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system associated with mitochondrial dysfunction and alterations in markers related to muscular and neural health. The aim of this study was to investigate the effect of eight weeks of neuromuscular training on serum levels of OPA1 and Atrogin-1 in patients with multiple sclerosis.
Methods:
This study was conducted as quasi-experimental applied research with a pretest–posttest design. The statistical population consisted of female patients with multiple sclerosis. The sample included 30 women who were selected through purposive and convenience sampling methods and were randomly assigned equally into two groups of 15 participants: 1) MS group (age: 37.10 ± 5.80 years, height: 160.70 ± 1.03 cm, weight: 58.20 ± 1.62 kg), and 2) MS + exercise group (age: 36.26 ± 5.90 years, height: 161.50 ± 1.42 cm, weight: 57.36 ± 1.63 kg). Neuromuscular training was performed for eight weeks, five sessions per week. The control group did not engage in any exercise during the study period. Blood samples were collected 24 hours before and 48 hours after the last training session, and the serum was used to measure OPA1 and Atrogin-1 levels. Data were analyzed using repeated-measures ANOVA at a 5% significance level using SPSS version 27.
Results:
The results showed that exercise had a significant reducing effect on OPA1 levels (p = 0.001, η² = 0.875) and Atrogin-1 levels (p = 0.001, η² = 0.682) in patients with MS.
Conclusion:
Eight weeks of neuromuscular training was associated with a significant reduction in OPA1 and Atrogin-1 levels in patients with MS. This suggests that neuromuscular training may improve neural health and reduce muscle atrophy in these patients. Therefore, neuromuscular training may be considered as a complementary approach in the management and faster recovery of patients with MS.
Keywords
Neuromuscular training
Atrophy markers
Multiple sclerosis
Subjects
  1. Ransohoff RM, Hafler DA & Lucchinetti CF. Multiple sclerosis- a quiet revolution. Nat Rev Neurol. 2015; 11(3): 134.
  2. Nakhzari Khodakheir J, Haghighi AH, Hamedinia MR. The effects of combined exercise training with aerobic dominant and coenzyme Q10 supplementation on Serum BDNF and NGF levels in patients with multiple sclerosis. J Arak Uni Med Sci. 2018; 21(3): 94-103. [Persian]
  3. Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann neurol. 2007; 61(4): 288-299.
  4. Ghadampour E, Radmehr P, Yousefvand L. The effectiveness of acceptance and commitment- based treatment on social competence and life expectancy of patients with multiple sclerosis.=Armaghane danesh. 2017; 21(11): 1100-1114.
  5. Raj, V. Importance of neuromuscular training of athletes. Int IJSS Sci. 2015; 5: 141-145.
  6. Gervasoni E, Beghi E, Corrini C, Parelli R, et al. Validity of 2 fall prevention strategy scales for people with stroke، parkinson's disease، and multiple sclerosis. J Geriatr Phys Ther. 2023; 46(1): 36-45.
  7. Zhang S, Yan H, Ding J, Wang R, et al. Skeletal muscle-specific DJ-1 ablation-induced atrogenes expression and mitochondrial dysfunction contributing to muscular atrophy. J Cachexia Sarcopenia Muscle. 2023; 14(5): 2126-2142.
  8. Nishimura Y, Chunthorng-Orn J, Lord S, Musa I, et al. Ubiquitin E3 ligase Atrogin-1 protein is regulated via the rapamycin-sensitive mTOR-S6K1 signaling pathway in C2C12 muscle cells. Am J Physiol Cell Physiol. 2022; 323(1): C215-C225
  9. Hazell G, McCallion E, Ahlskog N, Sutton ER, et al. Exercise, disease state and sex influence the beneficial effects of Fn14-depletion on survival and muscle pathology in the SOD1 G93A amyotrophic lateral sclerosis (ALS) mouse model. Skeletal Muscle. 2024 14; 14(1): 23
  10. Yu-Wai-Man P, Trenell MI, Hollingsworth KG, Griffiths PG, Chinnery PF. OPA1 mutations impair mitochondrial function in both pure and complicated dominant optic atrophy. Brain. 2011; 134(4): e164.
  11. Risbud M, Madhu V, Hernandez-Meadows M, Coleman A, et al. The loss of OPA1 accelerates intervertebral disc degeneration and osteoarthritis in aged mice. Res Sq. 2024.
  12. Méndez-López I, Sancho-Bielsa FJ, Engel T, García AG, Padín JF. Progressive mitochondrial SOD1G93A accumulation causes severe structural, metabolic and functional aberrations through OPA1 down-regulation in a mouse model of amyotrophic lateral sclerosis. Int J Mol Sc. 2021; 22(15): 8194
  13. Whitehead M, Harvey JP, Sladen PE, Becchi G, et al. Disruption of mitochondrial homeostasis and permeability transition pore opening in OPA1 iPSC-derived retinal ganglion cells. Acta Neuropathol Commun. 2025; 13(1): 28.
  14. Djalalvandi A, Takeda K, Grespi F, Fan H, et al. Opantimirs: A class of antagonizing microRNAs that upregulate Opa1 and improve mitochondrial and disuse myopathies. Cell Reports Med. 2025; 6(8).
  15. Sokhangu MK, Rahnama N, Etemadifar M, Rafeii M, Saberi A. Effect of neuromuscular exercises on strength, proprioceptive receptors, and balance in females with multiple sclerosis. Int J Prev Med. 2021;12
  16. Sokhangu MK, Rahnama N, Etemadifar M, Rafeii M, Saberi A. Effect of neuromuscular exercises on strength, proprioceptive receptors, and balance in females with multiple sclerosis. Int J Prev Med. 2021; 12: 5.
  17. Zhang L, He Z, Zhang Q, Wu Y, et al. Exercise pretreatment promotes mitochondrial dynamic protein OPA1 expression after cerebral ischemia in rats. Int J Mol Sci. 2014; 15(3): 4453-4463.
  18. Fry MY, Navarro PP, Hakim P, Ananda VY. In situ architecture of Opa1-dependent mitochondrial cristae remodeling. EMBO J. 2024; 43(3): 391.
  19. Yu-Wai-Man P, Spyropoulos A, Duncan HJ, Guadagno JV, Chinnery PF. A multiple sclerosis‐like disorder in patients with OPA1 mutations. Ann Clin Transl Neurol. 2016; 3(9):723-729.
  20. Caffin F, Prola A, Piquereau J, Novotova M. Altered skeletal muscle mitochondrial biogenesis but improved endurance capacity in trained OPA1‐deficient mice. The Journal of physiology. 2013 Dec 1;591(23):6017-37.
  21. Proschinger S, Kuhwand P, Rademacher A, Walzik D, et al. Fitness, physical activity, and exercise in multiple sclerosis: a systematic review on current evidence for interactions with disease activity and progression. J neurol. 2022; 269(6): 2922-2940.
  22. Nishimura Y, Chunthorng-Orn J, Lord S, Musa I, et al. Ubiquitin E3 ligase Atrogin-1 protein is regulated via the rapamycin-sensitive mTOR-S6K1 signaling pathway in C2C12 muscle cells. American Journal of Physiology-Cell Physiology. 2022; 323(1): C215-25.
  23. Gumucio JP, Mendias CL. Atrogin-1, MuRF-1, and sarcopenia. Endocrine. 2013; 43(1): 12-21.
  24. Bodine SC, Baehr LM. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab. 2014; 307(6): E469-E484.
  25. Liu W, Meng P, Li Z, Shen Y, et al. The multifaceted impact of physical exercise on FoxO signaling pathways. Frontiers in Cell and Developmental Biology. 2025; 13: 1614732.
Journal of Paramedical Sciences & Rehabilitation
Volume 15, Issue 2
Summer 2026
Pages 166-175