The Effect of Endurance Training on Fibronectin Gene Expression of the Sciatic Nerve in Diabetic Rats
Diabetic neuropathy can cause disorders in axon transmission, changes in the extracellular matrix, and peripheral nerve damages. However, its mechanism, along with the beneficial effects of exercise on these disorders is not entirely clear. The aim of the current study was to assess changes in fibronectin mRNA gene expression level of the sciatic nerve in rats with streptozotocin-induced diabetes after endurance training. Eighteen male Wistar rats (10 weeks old with 250±20 gr weight) were randomly assigned to three groups, including healthy, induced diabetes and induced diabetes plus endurance training. Induction of diabetes was conducted using an intraperitoneal injection of a single dose of streptozotocin (STZ). Neuropathy was confirmed using the behavioral tests. Rats in induced diabetes plus training group had 8 weeks of moderate and increasing intensity endurance training on the treadmill. The Fibronectin mRNA gene expression level of the sciatic nerve was assessed using Real-time-PCR. Changes in fibronectin protein and myelin thickness were measured by immunohistochemistry and luxol fast blue staining. The mean and standard deviation was used to report descriptive data. Data were entered into SPSS 22. Fibronectin mRNA gene expression level (1.90) of sciatic nerve fibronectin protein and myelin thickness reduced significantly due to diabetes (P<0.05). Eight weeks of endurance training increased fibronectin gene expression of sciatic nerve fibronectin protein and prevented further destruction of myelin, which was statistically significant. The results showed that diabetes leads to changes in the extracellular matrix and the reduction of the sciatic nerve myelin thickness. Endurance training as a non-drug strategy is effective in preventing these damages.
2- Fernyhough, P. (2015). Mitochondrial dysfunction in diabetic neuropathy: a series of unfortunate metabolic events. Current diabetes reports, 15(11), 89.
3- Vinik, A. I. , Casellini, C. , & Neuman, S. (2018). Diabetes and the Nervous System. Diabetes Complications, Comorbidities and Related Disorders, 1-82.
4- Singleton, J. R. , Smith, A. G. , & Marcus, R. L. (2015). Exercise as therapy for diabetic and prediabetic neuropathy. Current diabetes reports, 15(12), 120.
5- Cooper, M. A., Kluding, P. M., & Wright, D. E. (2016). Emerging relationships between exercise, sensory nerves, and neuropathic pain. Frontiers in neuroscience, 10, 372.
6- Barber, J. L. , Kraus, W. E. , Church, T. S. , Hagberg, J. M. , Thompson, P. D. , Bartlett, D. B. , . . . Landers-Ramos, R. Q. (2018). Effects of regular endurance exercise on GlycA: Combined analysis of 14 exercise interventions. Atherosclerosis, 277, 1-6.
7- Carsons, S. E. (2018). Fibronectin in health and disease: CRC Press.
8- Phillips, J. B. , King, V. R. , Ward, Z. , Porter, R. A. , Priestley, J. V. , & Brown, R. A. (2004). Fluid shear in viscous fibronectin gels allows aggregation of fibrous materials for CNS tissue engineering. Biomaterials, 25(14), 2769-2779.
9- Zhu, Y. , Soderblom, C. , Trojanowsky, M. , Lee, D. -H. , & Lee, J. K. (2015). Fibronectin matrix assembly after spinal cord injury. Journal of neurotrauma, 32(15), 1158-1167.
10-Ahmed, Z. , & Brown, R. A. (1999). Adhesion, alignment, and migration of cultured Schwann cells on ultrathin fibronectin fibres. Cell motility and the cytoskeleton, 42(4), 331-343.
11- King, V. , Phillips, J. , Hunt-Grubbe, H. , Brown, R. , & Priestley, J. (2006). Characterization of non-neuronal elements within fibronectin mats implanted into the damaged adult rat spinal cord. Biomaterials, 27(3), 485-496.
12- López-Álvarez, V. M. , Modol, L. , Navarro, X. , & Cobianchi, S. (2015). Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury. Pain, 156(9), 1812-1825.
13- Wilhelm, J. C. , Xu, M. , Cucoranu, D. , Chmielewski, S. , Holmes, T. , Lau, K. S. , . . . English, A. W. (2012). Cooperative roles of BDNF expression in neurons and Schwann cells are modulated by exercise to facilitate nerve regeneration. Journal of Neuroscience, 32(14), 5002-5009.
14- Heinemeier, K. , Langberg, H. , Olesen, J. L. , & Kjaer, M. (2003). Role of TGF-β1 in relation to exercise-induced type I collagen synthesis in human tendinous tissue. Journal of Applied Physiology, 95(6), 2390-2397.
15-Dandu, A. M. , & Inamdar, N. M. (2009). Evaluation of beneficial effects of antioxidant properties of aqueous leaf extract of Andrographis paniculata in STZ-induced diabetes. Pakistan journal of pharmaceutical sciences, 22(1).
16- Klopfenstein DR, Vale RD. The lipid binding pleckstrin homology domain in UNC-104 kinesin is necessary for synaptic vesicle transport in Caenorhabditis elegans. Mol Biol Cell 2004; 15(8): 3729-39.
17- Delcroix JD, Michael GJ, Priestley JV, Tomlinson DR, Fernyhough P. Effect of nerve growth factor treatment on p75NTR gene expression in lumbar dorsal root ganglia of streptozocin-induced diabetic rats. Diabetes
1998; 47(11): 1779-85.
18- Alrashdan MS, Sung MA, Kwon YK, Chung HJ, Kim SJ, Lee JH. Effects of combining electrical stimulation with BDNF gene transfer on the regeneration of crushed rat sciatic nerve. Acta Neurochir (Wien) 2011; 153(10): 2021-9.
19- Masoud Rahmati, Ali Khazani, Reza Gharakhanlou, MansourehMovaheddin , HomaManaheji. Chronic effects of moderate intensity endurance
training on neuropathic pain symptoms in diabetic rats. Physiol Pharmacol 2013 ;16:435- 445.
20- Chen YW, Li YT, Chen YC, Li ZY, Hung CH. Exercise training attenuates neuropathic pain and cytokine expression after chronic constriction injury of rat sciatic nerve. Anesth Analg 2012; 114(6): 1330-7.
21- Martino, M. M. , Briquez, P. S. , Ranga, A. , Lutolf, M. P. , & Hubbell, J. A. (2013). Heparin-binding domain of fibrin (ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix. Proceedings of the National Academy of Sciences, 110(12), 4563-4568.
22-Frantz, C. , Stewart, K. M. , & Weaver, V. M. (2010). The extracellular matrix at a glance. J Cell Sci, 123(24), 4195-4200.
23- Gardiner, N. J. (2011). Integrins and the extracellular matrix: key mediators of development and regeneration of the sensory nervous system. Developmental neurobiology, 71(11), 1054-1072.
24- Lefcort, F. , Venstrom, K. , McDONALD, J. A. , & Reichardt, L. F. (1992). Regulation of expression of fibronectin and its receptor, alpha 5 beta 1, during development and regeneration of peripheral nerve. Development, 116(3), 767-782.
25- Gardiner, N. J. , Moffatt, S. , Fernyhough, P. , Humphries, M. J. , Streuli, C. H. , & Tomlinson, D. R. (2007). Preconditioning injury-induced neurite outgrowth of adult rat sensory neurons on fibronectin is mediated by mobilisation of axonal α5 integrin. Molecular and Cellular Neuroscience, 35(2), 249-260.
26- Li, B. , Moshfegh, C. , Lin, Z. , Albuschies, J. , & Vogel, V. (2013). Mesenchymal stem cells exploit extracellular matrix as mechanotransducer. Scientific reports, 3, 2425.
27- Sawicka, K. M. , Seeliger, M. , Musaev, T. , Macri, L. K. , & Clark, R. A. (2015). Fibronectin interaction and enhancement of growth factors: importance for wound healing. Advances in wound care, 4(8), 469-478.
28- Hirsch, M. A. , van Wegen, E. E. , Newman, M. A. , & Heyn, P. C. (2018). Exercise-induced increase in brain-derived neurotrophic factor in human Parkinson's disease:a systematic review and meta-analysis. Translational neurodegeneration, 7(1), 7.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.