Journal of Eexercise & Organ Cross Talk

The effect of combined training (core stability, resistance and balance) on serum BDNF and GDNF levels in individuals with multiple sclerosis

Document Type : Original Article

Authors

1 PhD student, Department of Sports Physiology, Isf.C., Islamic Azad University, Isfahan, Iran

2 Associate Professor, Department of Sports Physiology, Faculty of Sports Sciences, Isf.C., Islamic Azad University, Isfahan, Iran

3 College of Physical Education and Sports Science, University of Al-Qadisiyah, Iraq

4 Professor, Department of Sports Physiology, Faculty of Sports Sciences, Isf.C., Islamic Azad University, Isfahan, Iran

5 Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract
Multiple sclerosis (MS) is a chronic neurological disease associated with neurodegeneration and impaired neurotrophic support. Neuromuscular training, through integrated activation of the nervous and muscular systems, may positively influence these neurotrophic factors. Therefore, this study investigated the effect of combined training on serum BDNF and GDNF levels in individuals with multiple sclerosis. Thirty women with multiple sclerosis (mean age: 36.2±5.8 years; BMI: 22.1±4.2 kg/m²) were purposively selected and randomly assigned to an experimental group (n=15) or a control group (n=15). The experimental group completed an eight-week combined training program (three sessions per week), consisting of core stability, resistance, balance, and agility exercises with progressive overload, while exercise intensity was controlled using the Borg perceived exertion scale., while the control group continued their usual daily activities. Blood samples were collected 24 hours before and 48 hours after the final training session, and the obtained serum was used to measure BDNF and GDNF levels. Data were analyzed using repeated-measures analysis of variance with a significance level of 0.05, employing SPSS software (version 27). The results demonstrated that neuromuscular training induced significant increases in serum BDNF (p=0.001, η²=0.80) and GDNF (p=0.001, η²=0.79) levels in the experimental group compared with the control group. Overall, the results of this study demonstrate that eight weeks of neuromuscular training elicit significant increases in serum BDNF and GDNF levels in women with multiple sclerosis. These findings indicate an enhanced neurotrophic environment that may support neural plasticity and neuroprotective mechanisms. Accordingly, neuromuscular training appears to be a safe and effective non-pharmacological strategy for improving neural health and potentially attenuating neurological dysfunctions associated with multiple sclerosis.

What is already known on this subject?

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and impaired neural signal transmission. This condition can lead to a wide range of symptoms, including muscle weakness, motor dysfunction, impaired balance, chronic fatigue, and cognitive deficits, ultimately affecting patients’ quality of life. Immune, genetic, and environmental factors play important roles in the onset and progression of MS, and evidence suggests that chronic inflammation and alterations in neurotrophic factors are key mechanisms involved in its pathophysiology.

 

What this study adds?

Combined training training, by simultaneously engaging the nervous and muscular systems, can play an effective role in modulating neurotrophic factors. Evidence suggests that this type of training, through increased targeted motor activity, improved neuromuscular coordination, and reduced neural stress, leads to enhanced expression and secretion of key neurotrophic factors such as BDNF and GDNF. Elevated levels of these factors may contribute to improved neuronal survival and plasticity, facilitation of neural repair, and strengthening of synaptic connections, ultimately resulting in improved neural and motor function, particularly in individuals with neurological disorders such as multiple sclerosis.

Keywords

Subjects

Acknowledgements

This article is derived from the master’s thesis conducted at the Islamic Azad University, Isfahan Branch. The authors would like to sincerely thank the Research Affairs of Islamic Azad University, Isfahan Branch, as well as all participants who kindly cooperated in the implementation of this study.

Funding

None.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Compliance with ethical standards

Conflict of interest the authors declare that there is no conflict of interest in the present research.

Ethical approval Given that the present study was conducted on human samples with exercise intervention over a relatively long period of time, in full compliance with the ethical principles of research, approval was received from the ethics committee with the ID number IR.IAU.KHUISF.REC.1404.525 from the Islamic Azad University, Isfahan (Khorasgan) Branch.

Informed consent Participants signed an informed consent form prior to participation in the study.

Author contributions 

Conceptualization: A.S.H., K.J,; Methodology: A.S.H., K.J.,F.T; Software: A.S.H., K.J; Validation: A.S.H., K.J.,F.T.AA.A; Formal analysis: K.J.; Investigation: A.S.H., K.J.,F.T.; Resources: A.S.H., K.J.,F.T.AA.A.; Data curation A.S.H., K.J.,F.T.; Writing - original draft: Z A.S.H., K.J.; Writing–review & editing: A.S.H., K.J.,F.T.; Visualization: A.S.H., K.J.,F.T.AA.A.; Supervision: K.J.; Project administration: A.S.H., K.J.; Funding acquisition: A.S.H.    

Airaksinen, M. S., & Saarma, M. (2002). The GDNF family: signalling, biological functions and therapeutic value. Nature Reviews Neuroscience, 3(5), 383-394. doi: https://doi.org/10.1038/nrn812  
Andreu-Caravaca, L., Ramos-Campo, D. J., Moncada-Jiménez, J., Abellán-Aynés, O., & Rubio-Arias, J. Á. (2025). Immediate and short-term effect of physical exercise on BDNF in multiple sclerosis patients: a systematic review and meta-analysis. Scientific reports, 15(1), 19696. doi: https://doi.org/10.1038/s41598-025-04675-0 
Bansi, J., Bloch, W., Gamper, U., & Kesselring, J. (2013). Training in MS: influence of two different endurance training protocols (aquatic versus overland) on cytokine and neurotrophin concentrations during three week randomized controlled trial. Multiple Sclerosis Journal, 19(5), 613-621. doi: https://doi.org/10.1177/1352458512458605  
Bansi J, B. W., Gamper U, Kesselring J. (2013). Training in MS: influence of two different endurance training protocols (aquatic versus overland) on cytokine and neurotrophinconcentrations during three week randomized controlled trial. Mult Scler, 19((5), 613-621. doi: https://doi.org/10.1177/1352458512458605  
Diechmann, M. D., Campbell, E., Coulter, E., Paul, L., Dalgas, U., & Hvid, L. G. (2021). Effects of exercise training on neurotrophic factors and subsequent neuroprotection in persons with multiple sclerosis—a systematic review and meta-analysis. Brain Sciences, 11(11), 1499.   
Gold SM, S. K., Hartmann S, et al. (2003). Basal serum levels and reactivity of nerve growth factor and brain-derived. Journal of neuroimmunology, 138, 99– 105. 
Farajnia, S., Rajabi, H., Ghaffari, M., Beladi-Moghadam, N., & Fayazmilani, R. (2025). Impact of cognitive-aerobic exercise training on brain-derived neurotrophic factor, dual-tasking abilities, and mood state in individuals with multiple sclerosis. Physiology & behavior, 290, 114756. doi: https://doi.org/10.1016/j.physbeh.2024.114756  
Huang, E. J., & Reichardt, L. F. (2001). Neurotrophins: roles in neuronal development and function. Annual review of neuroscience, 24(1), 677-736. doi: https://doi.org/10.1146/annurev.neuro.24.1.677 
Karimimoghadem, Z., Shafizadeh, A., & Ghasemi, B. (2023). Effect of 8 Weeks of Neuromuscular Training on Motor Function, Fatigue, and Quality of Life in Women with Multiple Sclerosis. Journal for Research in Sport Rehabilitation, 11(21), 119-129. 
Landers, J. B., Landers, K. R., & Young, N. G. (2025). The Effects of Blood Flow Restriction Exercise on Muscle–Brain Crosstalk: A Systematic Review. Muscles, 4(2), 19. doi:
Lee, J. J., Sitjar, P. H. S., Ang, E. T., & Goh, J. (2025). Exercise-induced neurogenesis through BDNF-TrkB pathway: implications for neurodegenerative disorders. Translational Exercise Biomedicine, 2(1), 21-29. doi:
Luo, S., Shi, L., Liu, T., & Jin, Q. (2025). Aerobic exercise training improves learning and memory performance in hypoxic-exposed rats by activating the hippocampal PKA–CREB–BDNF signaling pathway. BMC neuroscience, 26(1), 13. doi: https://doi.org/10.1186/s12868-025-00935-x  
Marzoli, F., Cardinali, L., Di Pinto, G., Campanella, M., Colombo, A., Ferrari, D., . . . Velardi, A. (2026). Physical Activity as a Tool for Social Inclusion in Multiple Sclerosis: A Systematic Review of Qualitative, Quantitative, and Mixed-Methods Evidence. Sports, 14(1), 25. doi:
Massah, Z., & Taghian, F. (2026). Impact of Soybean and Swimming Training Modifications on Inflammation, Neurogenesis and Cognitive Function in Polycystic Ovary Syndrome: Experimental and Bioinformatics Study. International Journal of Fertility and Sterility, 20(1), 34-49. doi: https://doi.org/10.22074/IJFS.2025.2039752.1750  
McCullough MJ, P. N., Kinnell KR,, & JM, S. (2011). Glial cell line-derived neurotrophic factor protein content in rat skeletal muscle is altered by increased physical activity in vivo and in vitro. Neuroscience, 3(174). doi: https://doi.org/10.1016/j.neuroscience.2010.11.016  
Oyovwi, M. O., Ogenma, U. T., & Onyenweny, A. (2025). Exploring the impact of exercise-induced BDNF on neuroplasticity in neurodegenerative and neuropsychiatric conditions. Molecular Biology Reports, 52(1), 140. doi: https://doi.org/10.1007/s11033-025-10248-1  
Prosperini, L., & Di Filippo, M. (2019). Beyond clinical changes: Rehabilitation-induced neuroplasticity in MS. Multiple Sclerosis Journal, 25(10), 1348-1362. 
Roh, H.-T., & So, W.-Y. (2017). The effects of aerobic exercise training on oxidant–antioxidant balance, neurotrophic factor levels, and blood–brain barrier function in obese and non-obese men. Journal of Sport and Health Science, 6(4), 447-453. doi: https://doi.org/10.1016/j.jshs.2016.07.006  
Schulz, K. F., Altman, D. G., & Moher, D. (2010). CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Journal of Pharmacology and pharmacotherapeutics, 1(2), 100-107. doi: https://doi.org/10.1186/1741-7015-8-18  
Soke, F., Kocer, B., Fidan, I., Keskinoglu, P., & Guclu-Gunduz, A. (2021). Effects of task-oriented training combined with aerobic training on serum BDNF, GDNF, IGF-1, VEGF, TNF-α, and IL-1β levels in people with Parkinson's disease: a randomized controlled study. Experimental gerontology, 150, 111384. doi: https://doi.org/10.1016/j.exger.2021.111384  
Taghizadeh, V., Hakak Dokht, E., & Ghahremani Moghaddam, M. (2021). Effect of 8 weeks of pilates training on serum level of brain-derived neurotrophic factor and dynamic balance in men with multiple sclerosis. Journal of Practical Studies of Biosciences in Sport, 9(18), 58-71. 
Tang, Z., Yin, M., Xu, K., Zheng, H., Yan, H., Zhao, Z., & Liu, Q. (2025). Exercise-Induced Changes in Brain-Derived Neurotrophic Factor in Neurodegenerative Diseases: A Bayesian Network Meta-Analysis. Journal of Geriatric Psychiatry and Neurology, 08919887251409415.  
Taube, W., Gruber, M., & Gollhofer, A. (2008). Spinal and supraspinal adaptations associated with balance training and their functional relevance. Acta physiologica, 193(2), 101-116. doi: https://doi.org/10.1111/j.1748-1716.2008.01850.x  
Wens C, K. N., Deck N,. (2016.). Brain derived neurotrophic factor in multiple sclerosis: effect of 24 weeks endurance and resistance training. European Journal of Neurology., 23, 1028–1035. doi: https://doi.org/10.1111/ene.12976   
Wrann, C. D., White, J. P., Salogiannnis, J., Laznik-Bogoslavski, D., Wu, J., Ma, D., . . . Spiegelman, B. M. (2013). Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell metabolism, 18(5), 649-659. URL: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(13)00377-X?cc=y    
Yucekaya, B., Kemer, S. N., Asan, E., Gerdan, H., Comuk Balci, N., Cakır, D., . . . Terzi, M. (2025). The effect of proprioceptive neuromuscular facilitation techniques on pain, motor functions, fatigue and health related quality of life in individuals with multiple sclerosis: a randomized, single-blind study. Neurological Research, 1-13. doi: https://doi.org/10.1080/01616412.2025.2490086  
Zhang, Z., & Huang, W. (2025). Exoskeleton robot gait training and its impact on the gut microbiota-brain axis in incomplete spinal cord injury patients: A narrative review of rehabilitation mechanisms. Journal of Multidisciplinary Healthcare, 6411-6430. doi: https://doi.org/10.2147/JMDH.S543841  
Volume 6, Issue 1
Winter 2026
Pages 25-32

  • Receive Date 04 December 2025
  • Revise Date 18 February 2026
  • Accept Date 21 February 2026