The effect of aerobic training along with resveratrol consumption on myostatin and IGF-1 levels in gastrocnemius muscle of rats after spinal cord injury

Document Type : Research Paper

Authors

Department of Physical Education, Bojnourd Branch, Islamic Azad University, Bojnourd, Iran.

10.22080/jaep.2024.26276.2167

Abstract

Objectives: Spinal cord injury (SCI) is associated with muscle atrophy. Therefore, the purpose of present study was to investigate the effect of aerobic training with resveratrol consumption on myostatin and insulin-like growth factor-1 (IGF-1) levels in the gastrocnemius muscles of rats after spinal cord injury.
Methods: thirty-six male Wistar rats aged eight weeks were placed in 4 groups including control, resveratrol, training and resveratrol + training. Spinal cord injury was caused by dropping a ten-gram weight from a height of 25 mm on the spinal cord in the T10 segment. Resveratrol supplement with a dose of 10 mg/kg was injected intraperitoneally and daily. The aerobic training was carried out with the help of the weight support system for 4 weeks, each session was 58 minutes and the intensity was 20 m/min. The level of myostatin and insulin-like growth factor-1 (IGF-1) levels in the gastrocnemius muscle were measured by ELISA method. To analyze the data, one-way analysis of variance and Tukey's post hoc test were used at the significance level of p<0.05.
Results: Myostatin level in gastrocnemius muscle of training and resveratrol groups did not show any difference compared to the control group, But Myostatin level in gastrocnemius muscle of training+resveratrol group was significantly lower than control group (p=0/045). IGF-1 level in gastrocnemius muscle of training and resveratrol groups did not show any difference compared to the control group, But IGF-1 level in gastrocnemius muscle of training+resveratrol group was significantly higher than control group (p=0/021).
Conclusion: it seems that aerobic training, when combined with resveratrol supplementation, can prevent atrophy caused by spinal cord injury in muscles below the injury level by affecting the level of muscle myostatin and IGF-1.

Keywords


##Abrigo, J., Simon, F., Cabrera, D., Vilos, C., & Cabello-Verrugio, C. (2019). Mitochondrial dysfunction in skeletal muscle pathologies. Current Protein and Peptide Science, 20(6), 536-546. ##Ahuja, C. S., Wilson, J. R., Nori, S., Kotter, M., Druschel, C., Curt, A., & Fehlings, M. G. (2017). Traumatic spinal cord injury. Nature reviews Disease primers, 3(1), 1-21. ##Alamdari, N., Aversa, Z., Castillero, E., Gurav, A., Petkova, V., Tizio, S., & Hasselgren, P.-O. (2012). Resveratrol prevents dexamethasone-induced expression of the muscle atrophy-related ubiquitin ligases atrogin-1 and MuRF1 in cultured myotubes through a SIRT1-dependent mechanism. Biochemical and biophysical research communications, 417(1), 528-533. ##Alvarez-Mejia, L., Morales, J., Cruz, G. J., Olayo, M.-G., Olayo, R., Díaz-Ruíz, A., . . . Morales-Guadarrama, A. (2015). Functional recovery in spinal cord injured rats using polypyrrole/iodine implants and treadmill training. Journal of Materials Science: Materials in Medicine, 26, 1-11. ##Astorino, T. A., Harness, E. T., & Witzke, K. A. (2015). Chronic activity-based therapy does not improve body composition, insulin-like growth factor-I, adiponectin, or myostatin in persons with spinal cord injury. The journal of spinal cord medicine, 38(5), 615-625. ##Baligand, C., Gilson, H., Menard, J., Schakman, O., Wary, C., Thissen, J.-P., & Carlier, P. (2010). Functional assessment of skeletal muscle in intact mice lacking myostatin by concurrent NMR imaging and spectroscopy. Gene therapy, 17(3), 328-337. ##Basso, D., Beattie, M., Bresnahan, J., Anderson, D., Faden, A., Gruner, J., Nockels, R. (1996). MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Journal of Neurotrauma, 13(7), 343-359. ##Byrnes, K. R., Fricke, S. T., & Faden, A. I. (2010). Neuropathological differences between rats and mice after spinal cord injury. Journal of Magnetic Resonance Imaging, 32(4), 836-846. ##Chaplin, A., Carpéné, C., & Mercader, J. (2018). Resveratrol, metabolic syndrome, and gut microbiota. Nutrients, 10(11), 1651. ##Chien, Y.-H., Han, D.-S., Hwu, W.-L., Thurberg, B. L., & Yang, W.-S. (2013). Myostatin and insulin-like growth factor I: potential therapeutic biomarkers for pompe disease. PloS one, 8(8), e71900. ##Coyoy-Salgado, A., Segura-Uribe, J. J., Guerra-Araiza, C., Orozco-Suárez, S., Salgado-Ceballos, H., Feria-Romero, I. A., Orozco-Barrios, C. E. (2019). The importance of natural antioxidants in the treatment of spinal cord injury in animal models: an overview. Oxidative medicine and cellular longevity, 2019: 12;2019:3642491. ##Feng, Y., He, Z., Mao, C., Shui, X., & Cai, L. (2019). Therapeutic effects of resveratrol liposome on muscle injury in rats. Medical science monitor: international medical journal of experimental and clinical research, 2:25:2377-2385. ##Girbovan, C., Kent, P., Merali, Z., & Plamondon, H. (2016). Dose-related effects of chronic resveratrol administration on neurogenesis, angiogenesis, and corticosterone secretion are associated with improved spatial memory retention following global cerebral ischemia. Nutritional Neuroscience, 19(8), 352-368. ##Gómara-Toldrà, N., Sliwinski, M., & Dijkers, M. P. (2014). Physical therapy after spinal cord injury: a systematic review of treatments focused on participation. The journal of spinal cord medicine, 37(4), 371-379. ##Gorgey, A., & Dudley, G. (2007). Skeletal muscle atrophy and increased intramuscular fat after incomplete spinal cord injury. Spinal Cord, 45(4), 304-309. ##Graham, Z. A., Collier, L., Peng, Y., Saéz, J. C., Bauman, W. A., Qin, W., & Cardozo, C. P. (2016). A soluble activin receptor IIB fails to prevent muscle atrophy in a mouse model of spinal cord injury. Journal of Neurotrauma, 33(12), 1128-1135. ##Han, D.-S., Hsiao, M.-Y., Wang, T.-G., Chen, S.-Y., & Yang, W.-S. (2016). Association of serum myokines and aerobic exercise training in patients with spinal cord injury: an observational study. BMC neurology, 16, 1-7. ##Han, D. S., Chen, Y. M., Lin, S. Y., Chang, H. H., Huang, T. M., Chi, Y. C., & Yang, W. S. (2011). Serum myostatin levels and grip strength in normal subjects and patients on maintenance haemodialysis. Clinical endocrinology, 75(6), 857-863. ##Hart, N., Sarga, L., Csende, Z., Koltai, E., Koch, L. G., Britton, S. L., Radak, Z. (2013). Resveratrol enhances exercise training responses in rats selectively bred for high running performance. Food and chemical toxicology, 61, 53-59. ##Harvey, L., Lin, C.-W., Glinsky, J., & De Wolf, A. (2009). The effectiveness of physical interventions for people with spinal cord injuries: a systematic review. Spinal Cord, 47(3), 184-195. ##Invernizzi, M., Carda, S., Rizzi, M., Grana, E., Squarzanti, D., Cisari, C., Renò, F. (2015). Evaluation of serum myostatin and sclerostin levels in chronic spinal cord injured patients. Spinal Cord, 53(8), 615-620. ##Jackson, J. R., Ryan, M. J., Hao, Y., & Alway, S. E. (2010). Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 299(6), 1572-1581. ##Jiang, Q., Cheng, X., Cui, Y., Xia, Q., Yan, X., Zhang, M., Huang, Y. (2019). Resveratrol regulates skeletal muscle fibers switching through the AdipoR1-AMPK-PGC-1α pathway. Food & Function, 10(6), 3334-3343. ##Krakoff, J., Funahashi, T., Stehouwer, C. D., Schalkwijk, C. G., Tanaka, S., Matsuzawa, Y., Knowler, W. C. (2003). Inflammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian. Diabetes care, 26(6), 1745-1751. ##Krause, M. P., Liu, Y., Vu, V., Chan, L., Xu, A., Riddell, M. C., Hawke, T. J. (2008). Adiponectin is expressed by skeletal muscle fibers and influences muscle phenotype and function. American Journal of Physiology-Cell Physiology, 295(1), 203-212. ##Lee, S.-J. (2007). Quadrupling muscle mass in mice by targeting TGF-ß signaling pathways. PloS one, 2(8), e789. ##Mañas-García, L., Denhard, C., Mateu, J., Duran, X., Gea, J., & Barreiro, E. (2021). Beneficial Effects of Resveratrol in Mouse Gastrocnemius: A Hint to Muscle Phenotype and Proteolysis. Cells, 10(9), 2436. ##Mañas-García, L., Guitart, M., Duran, X., & Barreiro, E. (2020). Satellite cells and markers of muscle regeneration during unloading and reloading: Effects of treatment with resveratrol and curcumin. Nutrients, 12(6), 1870. ##Marimuthu, K., Murton, A. J., & Greenhaff, P. L. (2011). Mechanisms regulating muscle mass during disuse atrophy and rehabilitation in humans. Journal of applied physiology, 110(2), 555-560. ##Mohan, S., & Baylink, D. (2002). Beyond carrier proteins: IGF-binding proteins are multifunctional and act via IGF-dependent and–independent mechanisms. J endocrinol, 175, 19-31. ##Mohr, T., Andersen, J. L., Biering-Sørensen, F., Galbo, H., Bangsbo, J., Wagner, A., & Kjaer, M. (1997). Long term adaptation to electrically induced cycle training in severe spinal cord injured individuals. Spinal Cord, 35(1), 1-16. Momken, I., Stevens, L., Bergouignan, A., Desplanches, D., Rudwill, F., Chery, I., Sebedio, J. L. (2011). Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat. The FASEB Journal, 25(10), 3646-3660##. Montesano, A., Luzi, L., Senesi, P., Mazzocchi, N., & Terruzzi, I. (2013). Resveratrol promotes myogenesis and hypertrophy in murine myoblasts. Journal of translational medicine, 11(1), 1-15. ##Mouisel, E., Relizani, K., Mille-Hamard, L., Denis, R., Hourdé, C., Agbulut, O., Vignaud, A. (2014). Myostatin is a key mediator between energy metabolism and endurance capacity of skeletal muscle. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 307(4), R444-R454. ##Otzel, D. M., Lee, J., Ye, F., Borst, S. E., & Yarrow, J. F. (2018). Activity-based physical rehabilitation with adjuvant testosterone to promote neuromuscular recovery after spinal cord injury. International Journal of Molecular Sciences, 19(6), 1701. ##Paoli, A., Pacelli, Q. F., Neri, M., Toniolo, L., Cancellara, P., Canato, M., Faggian, D. (2015). Protein supplementation increases postexercise plasma myostatin concentration after 8 weeks of resistance training in young physically active subjects. Journal of medicinal food, 18(1), 137-143. ##Rodriguez, J., Vernus, B., Chelh, I., Cassar-Malek, I., Gabillard, J.-C., Sassi, A. H., Bonnieu, A. (2014). Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cellular and Molecular Life Sciences, 71(22), 4361-4371. ##Sahebkar, A., Serban, C., Ursoniu, S., Wong, N. D., Muntner, P., Graham, I. M., Sperling, L. S. (2015). Lack of efficacy of resveratrol on C-reactive protein and selected cardiovascular risk factors—Results from a systematic review and meta-analysis of randomized controlled trials. International journal of cardiology, 189, 47-55. ##Samarghandian, S., Pourbagher-Shahri, A. M., Ashrafizadeh, M., Khan, H., Forouzanfar, F., Aramjoo, H., & Farkhondeh, T. (2020). A pivotal role of the nrf2 signaling pathway in spinal cord injury: A prospective therapeutics study. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), 19(3), 207-219. ##Sandrow-Feinberg, H. R., Izzi, J., Shumsky, J. S., Zhukareva, V., & Houle, J. D. (2009). Forced exercise as a rehabilitation strategy after unilateral cervical spinal cord contusion injury. Journal of Neurotrauma, 26(5), 721-731. ##Schiaffino, S., Reggiani, C., Akimoto, T., & Blaauw, B. (2021). Molecular mechanisms of skeletal muscle hypertrophy. Journal of neuromuscular diseases, 8(2), 169-183. ##Schoenfeld, A. J., Laughlin, M. D., McCriskin, B. J., Bader, J. O., Waterman, B. R., & Belmont Jr, P. J. (2013). Spinal injuries in United States military personnel deployed to Iraq and Afghanistan: an epidemiological investigation involving 7877 combat casualties from 2005 to 2009. Spine, 38(20), 1770-1778. ##Shyu, K.-G., Ko, W.-H., Yang, W.-S., Wang, B.-W., & Kuan, P. (2005). Insulin-like growth factor-1 mediates stretch-induced upregulation of myostatin expression in neonatal rat cardiomyocytes. Cardiovascular research, 68(3), 405-414. ##Talmadge, R., Castro, M., Apple Jr, D., & Dudley, G. (2002). Phenotypic adaptations in human muscle fibers 6 and 24 wk after spinal cord injury. Journal of applied physiology, 92(1), 147-154. ##Xu, X., Talifu, Z., Zhang, C.-J., Gao, F., Ke, H., Pan, Y.-Z., Jing, Y.-L. (2023). Mechanism of skeletal muscle atrophy after spinal cord injury: A narrative review. Frontiers in Nutrition, 10. ##Ye, F., Baligand, C., Keener, J. E., Vohra, R., Lim, W., Ruhella, A., Thompson, F. (2013). Hindlimb muscle morphology and function in a new atrophy model combining spinal cord injury and cast immobilization. Journal of Neurotrauma, 30(3), 227-235. ##Yin, L., Li, N., Jia, W., Wang, N., Liang, M., Yang, X., & Du, G. (2021). Skeletal muscle atrophy: From mechanisms to treatments. Pharmacological research, 172, 105807. ##