Document Type : Research Paper

Authors

Abstract

The aim of present study was to investigate the effect of 6 weeks of endurance training on gene expression of Brain Derived Neurotrophic Factor (BDNF) sensory roots of sciatic nerve in rats with diabetic neuropathy. Twenty-eight adult male Wistar rats in the body mass range of 326/3±8/4 gr, randomly assigned in to four groups: diabetic control, diabetic training, healthy control and healthy training. For inducing diabetic neuropathy, after twelve hours of food starvation, intraperitoneal injection of STZ solution (45 mg/Kg) method was used. Two weeks after STZ injection, the endurance training protocol was performed for six weeks and Twenty-four hours after the last training session, rats were sacrificed. Real-Time PCR was used for BDNF gene expression measurement. For data Analysis, Kruskal– Wallis and Mann-Whitney U Test were used (P≤0.05). Results indicate that diabetes decreases BDNF expression (10-folds) in sensory roots of sciatic nerve. However, 6 weeks of endurance training can partly compensate the BDNF expression decrease induced by diabetic neuropathy (P=0.043). This study shows that diabetes can decrease BDNF expression in sensory roots of sciatic nerve. however, this decrease can be reversible some deal by endurance. In summary, result of this study support this hypothesis that neurotrophic support decreases in diabetic neuropathy.

Keywords

Main Subjects

1) Feldman E L, Stevens M J, Russell J W, Greene D A. Diabetic neuropathy. In. Current Review of Diabetes. S. Taylor (Ed.). Current Medicine. Philadelphia; 1999. pp: 71–83.
2) Schmeichel A M, Schmelzer J D, Low P A. Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy. Diabetes. 2003; 52:165–71.
3) Leinninger G M, Vincent AM and Feld EL. The role of growth factors in diabetic peripheral neuropathy. Journal of the Peripheral Nervous System. 2004; 9: 26–53.
4) Hellweg R, Hartung H D. Endogenous levels of nerve growth factor (NGF) are altered in experimental diabetes mellitus: A possible role for NGF in the pathogenesis of diabetic neuropathy. J Neurosci Res. 1990; 26: 258–67.
5) Kasayama S, Oka T. Impaired production of nerve growth factor in the submandibular gland of diabetic mice. Am J Physiol. 1989; 257: 400–4.
6) Nagahara A H, Tuszynski M H. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov. 2011; 10: 209–19.
7) Vavrek R, Pearse D D, Fouad K. Neuronal populations capable of regeneration following a combined treatment in rats with spinal cord transection. J Neurotrauma. 2007; 24: 1667–73.
8) Foster E, Robertson B, Fried K. TRKB-like immunoreactivity in rat dorsal root ganglia following sciatic nerve injury. Brain Res. 1994; 659: 267–71.
9) Ha S O, Kim J K, Hong H S, Kim D S, Cho H J. Expression of brain-derived neurotrophic factor in rat dorsal root ganglia, spinal cord and gracile nuclei in experimental models of neuropathic pain. Neuroscience. 2001; 107:301–9.
10) Mizisin A P, Bache M, DiStefano P S, Acheson A, Lindsay R M, Calcutt N A. BDNF attenuates functional and structural disorders in nerves of galactose-fed rats. J Neuropathol Exp Neurol. 1997; 56: 1290–301.
11) Sobue G, Yamamoto M, Doyu M, Li M, Yasuda T, Mitsuma T. Expression of mRNAs for neurotrophins (NGF, BDNF, and NT-3) and their receptors (p75NGFR, trk, trkB, and trkC) in human peripheral neuropathies. Neurochem Res. 1998; 23: 821–9.
12) Weis J, Saxena S, Evangelopoulos ME and Kruttgen A. Trophic factors in neurodegenerative disorders. IUBMB Life. 2003; 55(6): 353–7.
13) Gomez-Pinilla F, Ying Z, Roy R R, Molteni R, Edgerton V R. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol. 2002; 88: 2187–95.
14) Adlard P A, Perreau V M, Engesser-Cesar C, Cotman C W. The time course of induction of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus following voluntary exercise. Neurosci Lett. 2004; 363: 43–8.
15) برزگر حامد، وسدی الهام، برجیان‌فرد محبوبه. تأثیر تمرین­های متفاوت ورزشی بر مقادیر عامل نوروتروفیک مشتق از مغز در موش­های صحرایی. نشریۀ فیزیولوژی ورزش. 1393؛ (24): 180ـ99.
16) میرزایی سعید، فلاح‌محمدی ضیا، حاجی‌زاده مقدم اکبر، فتحی رزیتا، علیزاده رستم، رنجبر روح‌الله. اثر 8 هفته تمرین استقامتی با مدت‌های مختلف بر سطوح فاکتورهای نوروتروفیک مشتق از مغز در پلاسمای موش‌های صحرایی نر. نشریۀ پژوهش در علوم ورزشی. 1390؛ (10): 28ـ115.
17) فلاح‌محمدی ضیا، نظری حسین. تأثیر 4 هفته تمرین پلیومتریک بر غلظت سرمی فاکتور نروتروفیک مشتق از مغز مردان فعال. نشریۀ فیزیولوژی ورزشی. 1392؛ (20): 38ـ29.
18) Deschenes M R, Tenny K A, Wilson M H. Increased and decreased activity elicits specific morphological adaptations of the neuromuscular junction. Neuroscience. 2006; 137: 1277–83.
19) Zhang J Y, Luo X G, Xian C J, Liu Z H, Zhou X F. Endogenous BDNF is required formyelination and regeneration of injured sciatic nerve in rodents. Eur J Neurosci. 2000; 12: 4171–80.
20) Calcutt N. Modeling diabetic sensory neuropathy in rats. In Z. D. Luo (Ed.). Pain research methods in molecular medicine. Humana Press. 2004; 99: 55-65.
21) Rajasekar R, Manokaran K, Rajasekaran N, Duraisamy G and Kanakasabapathi D. Effect of Alpinia calcarata on glucose uptake in diabetic rats-an in vitro and in vivo model. Journal of Diabetes & Metabolic Disorders. 2014; 33(13): 1-13.
22) Chae C H, Jung S L, An S H, Jung C K, Nam S N, Kim H T. Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats. J Physiol Biochem. 2011; 67(2): 235-41.
23) Ghanbari-Niaki A, Khabazian B M, Hossaini-Kakhak S A, Rahbarizadeh F, Hedayati M. Treadmill exercise enhances ABCA1 expression in rat liver. Biochemical and Biophysical Research Communications. 2007; 361, 841–6.
24) Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988; 32(1): 77-88.
25) Talbot S, Théberge-Turmel P, Liazoghli D, Sénécal J, Gaudreau P, Couture R. Cellular localization of kinin B1 receptor in the spinal cord of streptozotocin-diabetic rats with a fluorescent. Journal of Neuroinflammation. 2009; 6-11. DOI: 10.1186/1742-2094-6-11
26) Tal M, Bennett G J. Extra-territorial pain in rats with a peripheral mononeuropathy: Mechano-hyperalgesia and mechano-allodynia in the territory of an uninjured nerve. Pain. 1994; 57(3): 375-82.
27) Christ-Roberts C Y‌, Pratipanawatr T‌, Pratipanawatr W‌, Berria R, Belfort R, Kashyap S, et al. Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signaling in overweight nondiabetic and type 2 diabetic subjects. Metabolism. 2004; 53: 1233–42.
28) Sriwijitkamol A‌, Coletta D‌, Estela W‌, Gabriela B‌, Sara M‌, John B‌, et al. Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: A time-course and dose-response study‌. Diabetes. 2007; 56: 836 –48.
29) Andreassen C S, Jakobsen J, Flyvbjerg A, Andersen H. Expression of neurotrophic factors in diabetic muscle- relation to neuropathy and muscle strength. Brain. 2009: 132; 2724–33.
30) Boucek P. Advanced diabetic neuropathy: A point of no return? Rev Diabet Stud. 2006; 3(3): 7.
31) Yasuda H, Terada M, Maeda K, Kogawa S, Sanada M, Haneda M, et al. Diabetic neuropathy and nerve regeneration. Progress in Neurobiology. 2003; 69(4): 229-85.
32) Fernyhough P, Diemel L T, Tomlinson D R. Target tissue production and axonal transport of neurotrophin- 3 are reduced in streptozocin-diabetic rats. Diabetologia. 1998; 41: 300–6.
33) Fernyhough P, Diemel L T, Hardy J, Brewster W J, Mohiuddin L, Tomlinson D R. Human recombinant nerve growth factor replaces deficient neurotrophic support in the diabetic rat. Eur J Neurosci. 1995; 7: 1107–10.
34) Acheson A, Conover J C, Fandl J P, DeChiara T M, Russell M, Thadani A, et al. A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature. 1995; 374:  450–3.
35) Karchewski L A, Kim F A, Johnston J, McKnight R M, Verge V M. Anatomical evidence supporting the potential for modulation by multiple neurotrophins in the majority of adult lumbar sensory neurons. J Comp Neurol. 1999; 413: 327–41.
36) Wetmore C, Olson L. Neuronal and nonneuronal expression of neurotrophins and their receptors in sensory and sympathetic ganglia suggest new intercellular trophic interactions. J Comp Neurol. 1995; 353: 143–59.
37) Willis D, Li K W, Zheng J Q, Chang J H, Smit A, Kelly T, et al. Differential transport and local translation of cytoskeletal, injury-response, and neurodegeneration protein mRNAs in axons. J Neurosci. 1995; 25: 778–91.
38) Perlson E, Hanz S, Medzihradszky K F, Burlingame A L, Fainzilber M. From snails to sciatic nerve: Retrograde injury signaling from axon to soma in lesioned neurons. J Neurobiol. 2004; 58: 287–94.
39) Zhan W Z, Mantilla C B, Sieck G C. Regulation of neuromuscular transmission by neurotrophins. Acta Physiologica Sinica. 2003; 55(6): 617-24.
40) Van Praag H, Christie B, Sejnowski T, Gage F. Running enhances neurogenesis, learning and long - term potentiaton in mice. Proc Natl Acad Sci USA. 1999; 96:        13427-31.
41) Gold S M, Schulz K, Hartmann S, Mladek M, Lang U, Hellweg R, et al. Basal serum levels and reactivity of nerve growth factor and brain derived neruotropic factor to standardized acute exercise in multiple sclerosis and controls. J Neuroimmunol. 2003; 138: 99-105.
42) Egan M F, Kojima M, Calicott J H, Goldberg T E, Kolachana B S, Bertolino A, et al. BDNF val66 net polymorphism affects activity – dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003; 112: 257-69.