Document Type : Research Paper

Authors

1 Ph.D Student of Exercise Physiology, Sari Branch, Islamic Azad University, Sari, Iran

2 Assistant Professor of Exercise Physiology, Sari Branch, Islamic Azad University, Sari, Iran

3 Professor of Cellular and Molecular Biology, Babol University of Medical Sciences, Babol, Iran

Abstract

The purpose of this study was to investigate the effect of 6 weeks progressive aerobic training with tail injection of adipose tissue-derived stem cells on nerve growth factor (NGF and vascular endothelial growth factor (VEGF( levels in streptozotocin-Induced diabetic rat’s hippocampus. 48 rats (weight: 220-240 g and age: 9 week) were divided into 6 groups: control, sham ،control diabetes, diabetes+exercise, diabetes + stem cell, diabetes + exercise + stem cell. The exercise protocol was treadmill running for 5 days per week with intensity of 60-70% VO2max for 6 weeks. In the stem cell receiver group, Insulin Syringes with PBS / 5 ml contains 1/5*106 number of stem cells extracted from human adipose tissue of diabetic rats was injected into the tail vein. Diabetes was induced by injection of streptozotocin (60 mg/kg) dissolved in citrate buffer, pH 4.5 intraperitoneally. VEGF and NGF levels in the hippocampus were measured by ELISA. The levels of VEGF and NGF were significantly reduced in the diabetic group compared to the control (P = 0.0001). On the other hand, VEGF levels in the diabetic + exercise + cell group were significantly higher than other groups (P = 0.0001). Also, these levels were significantly increased in the diabetes + cell and diabetes + exercise groups compared with the control diabetes group(P = 0.0001). On the other hand, the level of NGF in the diabetic cell group was significantly higher than that of the other groups except for the group of diabetes (P = 0.0001). Also, these levels were significantly increased in the diabetes + cell and diabetes + exercise groups compared with the control diabetes group (P = 0.0001). Generally, the results showed that the levels of NGF and VEGF in the training group, stem cell and also in the combined group were significantly increased compared to the control group for diabetes. Therefore, it seems that each of the interventions, especially their combination, can be a controller factor against diabetes due to an increase in neurotrophic and vascular effects.

Keywords

Main Subjects

  1. Havilah P, Pandit Vinodh B, Durga Prasad K. Adenosine deaminase activity in type-2 diabetes mellitus: An independent marker of glycemic status and stimulator of lipid peroxidation. Int J Chem. 2013;2(6):1175-8.
  2. Knopman D, Boland LL, Mosley T, Howard G, Liao D, Szklo M, et al. Atherosclerosis risk in communities (ARIC) study investigators. Cardiovascular risk factors and cognitive decline in middle-aged adults. Neurology. 2001;56:42–8.
  3. Gispen WH, Biessels GJ. Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci. 2000;23:542–9.
  4. Sun MK, Alkon DL. Link between Alzheimer’s disease and diabetes. Drugs Today 2006, 42(7): 481.
  5. Baydas G, Nedzvetskii VS, Nerush PA, Kirichenko SV, Yoldas T. Altered expression of NCAM in hippocampus and cortex may underlie memory and learning deficits in rats with streptozocin-induced diabetes mellitus. Life Science. 2003;73:1907-16.
  6. Pedersen BK, Pedersen M, Krabbe KS, Bruunsgaard H, Matthews VB, Febbraio MA. Role of exercise-induced bdnf production in the regulation of energy homeostasis. Exp Physiol. 2009;94:1153-60.
  7. Fang Yu, Kolanowski Ann. Facilitating aerobic exercise training in older adults with Alzheimer s disease. Geriatr Nurs. 2009;30)4):250-9.
  8. Winter B, Breitenstein C, Mooren FC, Voelker K, Fobker M, Lechtermann A. High impact ruuning improves learning. Neurobiol Learn Mem. 2007;87:597-609.
  9. Momeni Z, Behnam Rasoli M, Feridoni M. Comparison of the effects of type 1 and type 2 diabetes on hippocampal neuronal density in male Wistar rats. Iran. J. Diabetes Lipid Disord. 2011;10(4):339-46. (In Persian).
  10. Reagan LP. Insulin signaling effects on memory and mood. Curr Opin Pharmacol. 2007;7:633-7.
  11. Jafari Anarkooli I, Sankian M, Varasteh aAR, Haghir H. Effects of insulin and ascorbic acid on inhibition of the apoptosis in hippocampus of stz-induced diabetic rats. Anat Sci J. 2010;7:133-43. (in Persian).
  12. Xu B, Zang K, Ruff NL, Zhang YA, McConnell SK, Stryker MP. Cortical degeneration in the absence of neurotrophin signaling: Dendritic retraction and neuronal loss after removal of the receptor TrkB. Neuron. 2000;26:233-45.
  13. Hamidi Perchikolaei O, Fallah Mohammadi Z, Haji Zadeh Moghadam A. The effect of treadmill running with consumption of vitamin D3 on NGF levels in Parkinsonian rat’s striatum. Sport Physiol. 2016; 8(29): 91-102. (In Persian).
  14. 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;47:1779-85.
  15. 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 pphosphatidylinositol 3-kinase activation in thesoleus of diabetic rats. J Physiol Biochem. 2011;67:235-41.
  16. Aloe L, Rocco M, Bianchi P, Manni L. Nerve growth factor: From the early discoveries to the potential clinical use. J. Transl. Med. 2012;10:239-54.
  17. Tesfaye S, Malik R, Ward JD. Vascular factors in dabetic neuropathy. Diabetologia. 1994;37:847-57.
  18. Al-Jarrah M, Jamous M, Al Zailaey K, Bweir SO. Endurance exercise training promotes angiogenesis in the brain of chronic/progressive mouse model of Parkinson's Disease. NeuroRehabilitation. 2010; 26(4):369-73.
  19. Tavakkoly BJ, Pravica V, Boulton AJ, Hutchinson IV. Genetics of diabetic neuropathy: Study of VEGF gene. ijdld. 2005;5(2):117-25.
  20. De Salles Bf, Simão R, Fleck SJ, Dias I, Kraemer-Aguiar LG, Bouskela E. Effects of resistance training on cytokines. Int J Sports Med. 2010;31(7):441-50.
  21. Tang Z, Yuan L, Gu C, Liu Y, Zhu L. Effect of exercise on the expression of adiponectin mRNA and GLUT4 mRNA in type 2 diabetic rats. J Huazhong Univ Sci Technolog Med Sci. 2005;25(2):191-3.
  22. Tokmakidis SP, Zois CE, Volaklis KA, Kotsa K, Touvra AM. The effects of a combined strength and aerobic exercise program on glucose control and insulin action in women with type 2 diabetes. Eur J Appl Physiol. 2004; 92(4-5):437-42.
  23. Boulé NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: A meta-analysis of controlled clinical trials. JAMA. 2001;286(10):1218-27.
  24. Sheu WH, Chang TM, Lee WJ, Ou HC, Wu CM, Tseng LN, et al. Effect of weight loss on proinflammatory state of mononuclear cells in obese women. Obesity (Silver Spring). 2008;16(5):1033-8.
  25. Eizadi M, Behboudi L. Effect of acute and chronic exercise on beta-cell function in diabetic patients. JKH. 2012;6(4):15-19. (In Persian).
  26. Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: Key roles of growth factor cascades and inflammation. Trends Neurosci. 2007;30(9):464-72.
  27. Villar-Cheda B, Sousa-Ribeiro D, Rodriguez-Pallares J, Rodriguez-Perez AI, Guerra MJ, Labandeira-Garcia JL. Aging and sedentarism decrease vascularization and VEGF levels in the rat substantia nigra. Implications for Parkinson's disease. J. Cereb. Blood Flow Metab. 2008;29(2):230-4.
  28. Wahl P, Jansen F, Achtzehn S, Schmitz T, Bloch W, Mester J, Werner N. Effects of high intensity training and high volume training on endothelial microparticles and angiogenic growth factors. PLoS One. 2014;9(4):96024.
  29. Priscylla N, Pamela B, Fabiana G, Larissa B, Patrícia, S. Physical exercise reverses spatial memory deficit and induces hippocampal astrocyte plasticity in diabetic rats. Brain Res. 2017;1655)15:(242-51.
  30. Pourheydar B, Shahi M, Farjah GH. Evaluation of apoptosis in hippocampal cells of rat following in travenous injection of bone marrow stromal cells in ischemia-reperfusion. Urmia Med J. 2014; 25(7):584-97. (In Persian).
  31. Guo F, Lv S, Lou Y, Tu W, Liao W, Wang Y, et al. Bone marrow stromal cells enhance the angiogenesis in ischaemic cortex after stroke: Involvement of notch signalling. Cell Biol Int. 2012;36(11):997–1004.
  32. Moradi A, Mohammadi S, Hamidi Alamdari D. Effect of adipose tissue-derived stem cells on the control of the blood glucose level in diabetic rats. J Shahid Sadoughi Univ Med Sci. 2015;23(8):717-26. (In Persian).
  33. Krishna KA, Rao GV, Rao KS. Stem cell-based therapy for the treatment of Type 1 diabetes mellitus. Regenerative Med. 2007;2(2):171-77.
  34. Lock LT, Tzanakakis ES. Stem/Progenitor cell sources of insulin-producing cells for the treatment of diabetes. Tissue Eng. 2007;13(7):1399-412.
  35. Chen Q, Lon, Y yuan X, Zou L, Sun J. protective effects of bone marrow stromal cell transplantation in injured rodent brain: Synthesis of neurotrophic factors. J Neurosci Res. 2005;80:611-9.
  36. Chae CH, Jung SL, An SH, Park BY, Wang SW, Cho IH, et al. Treadmill exercise improves cognitive function and facilitates nerve growth factor signaling by activating mitogen-activated protein kinase/ extracellular signalregulated kinase1/2 in the streptozotocin-induced diabetic rat hippocampus. Neuroscience. 2009;164:1665–73.
  37. Taha MF, Hedayati V. Isolation, identification and multipotential differentiation of mouse adipose tissue derived stem cells. Tissue Cell. 2010;42(4):211-16.
  38. Chae CH, Kim HT. Forced moderate-intensity treadmill exercise suppresses appotosis by increasing the level of NGF and stimulating phosphatidy linositol 3-kinase signaling in the hippocampus of induced aging rats. Neurochem Int. 2009;55(4):208-13.
  39. Capitelli CS, Lopes CS, Alves AC, Barbiero J, Oliveira LF, Silva VJ, et al. Opposite effects of bone marrow-derived cells transplantation in MPTP-rat model of Parkinson’s disease: A comparison study of mononuclear and mesenchymal stem cells. Int. J. Med. Sci. 2014;11(10):1049-64.
  40. Kang X, Huadong X, Sasa T, Xiaoyu Z, Zijun D, Li Z. Dopamine release from transplanted neural stem cells in Parkinsonian rat striatum in vivo. Pnas. 2014;111(44):15804-9.
  41. Hashemvarzi SA, Heidarianpour A. Preconditioning effect of aerobic exercise with D3 vitamin consumption on VEGF levels in the 6-OHDA lesioned Parkinson's disease rat model. Sport Physiol. 2016;8(30):129-42. (In Persian).
  42. Chae C-H, Lee H, Jung S, Kim T, Kim J, Kim N.  Swimming exercise increases the level of nerve growth factor and stimulates neurogenesis in adult rat hippocampus. Neuroscience. 2012;212:30-7.
  43. Nourshahi M, Taheri chadorneshin H, Ranjbar K. The stimulus of angiogenesis during exercise and physical activity. Q. Horiz. Med. Sci. 2013;18(5):286-96. (In Persian).
  44. Cadet J, Last R, Osticv K, Rezedborski P, Lewis VJ. Long term behavioral and biochemical effect of 6-OHDA injection in Rat Caudate Putamen. Brain Res Ball. 1991;26:707-13.
  45. Jalali Z, Dabidi Roshan V. The effect of regular endurance exercises and galbanum supplement on vascular function during chronic hypertension in male wistar rats. J. Sport Bio. 2014;6(1):95-113. (In Persian).
  46. Cawthorn WP, Scheller ES, MacDougald OA. Adipose tissue stem cells: The great WAT hope. Trends Endocrinol Metab. 2012;23(6):270–7.
  47. Caporali A, Emanueli C. Cardiovascular Actions of Neurotrophins. Physiol Rev. 2009;89:279–308.