Document Type : Research Paper

Authors

1 Ph.D Student of Exercise Physiology, Bu-Ali Sina University, Hamedan, Iran

2 Associate Professor of Exercise Physiology, Bu-Ali Sina University, Hamedan, Iran

3 Associate Professor of Exercise Physiology, University of Mazandaran

4 Professor of Cellular and Molecular Research Center, Babol University of Medical Sciences, Mazandaran, Iran

Abstract

Stem cells transplantation and exercise training are including of Non-drug treatment option that have been considered for the treatment of Parkinson's disease. The purpose of this study was to investigate the effect of 8 weeks aerobic training on striatum VEGF and DA levels in parkinsonian rats after transplantation of bone marrow stem cells. 35 male rats with the age of 7 weeks and weight 250-300 gr, were divided randomly into healthy control group and parkinsonian groups included of control, cell treatment, Exercise and cell treatment + Exercise. To create a model of Parkinson's, the striatum was destroyed by 6-hydroxy-dopamine injection into the striatum through stereotaxic apparatus and then was used apomorphine rotational test for confirm it. For isolation of bone marrow stem cells, bone marrow of femur and tibia of male rats 6-8 weeks were used. After cultivation, approximately 105 cells in 2 microliter of medium were injected through the channel into the striatum of cell recipient groups. ٍExercise was included 8 weeks of running on the treadmill with a speed of 15 meters per minute in 2 bouts for 5 days in per week. VEGF and DA measured by ELISA method. The results show that, striatum VEGF and DA levels increased significantly in Exercise, Stem cells and specially Stem cells + Exercise groups related to Parkinson group (P≤0.05). Generally, the results of this study approved the positive effect of 8 weeks treadmill exercise in parkinsonian rats after bone marrow stem cell transplantation which can be considered as a non-drug therapeutic manner in Parkinson’s disease.

Keywords

Main Subjects

1. Zigmond M J, Smeyne R J. Exercise: Is it a neuroprotective and if so, how does it work? Parkinsonism & Related Disorders. 2014; 20(3): 123-‌7.
2. Young H E, Hyer L, Black Jr A C, Robinson Jr J S. Treating Parkinson disease with adult stem cells. J Neurol Disord. 2013; 1(2): 1-8.
3. Haji Ghasem Kashani M, Ghorbanian M T, Hosseinpour L. Transplantation of deprenyl-induced Tyrosine hydroxylase-positive cells improves 6-OHDA-l‌esion rat m‌odel of Parkinson’s disease: Behavioral and immunohistochemical evaluation. Cell Journal (Yakhteh). 2013; 15(1): 55-64. (In Persian).
4. Han SC, Mal SS, Wook S, Tae-WJ, Baek VL, Young PK, et al. Treadmill exercise alleviates short-term memory impairment in 6-hydroxydopamine-induced Parkinson’s rats. Journal of Exercise Rehabilitation. 2013; 9(3): 354-‌61.
5. Anstrom KK, Schallert T, Woodlee MT, Shattuck A, Roberts D. Repetitive vibrissae-elicited forelimb placing before and immediately after unilateral 6-hydroxydopamine improves outcome in a model of Parkinson's disease. Behavioral Brain Research. 2007; 179(2): 183-‌91.
6. Choe M‌, Koo BS‌, An‌ ‌GJ‌, Jeon S. Effects of treadmill ‌exercise on the recovery of ‌dopaminergic neuron loss and muscle atrophy in the 6-OHDA lesioned Parkinson's disease rat model. The Korean Journal of Physiology & Pharmacology. 2012; 16(5): 305-‌12.
7. Wang T, Liu Y, Wang X, Yang N, Zhu H, Zuo Ping P. Protective effects of octacosanol on 6-hydroxydopamine-induced Parkinsonism in rats via regulation of ProNGF and NGF signaling. Acta Pharmacologica Sinica. 2010; 31(4): 765–‌74.
8. Chitsaz A, Maracy M, Basiri K, Izadi Boroujeni M, Tanhaei A P, Rahimi M, et al. 25-hydroxyvitamin D and severity of Parkinson’s disease. International Journal of Endocrinology. 2013; 10(11): 1-4. (In Persian).
9. Fallah-Mohammadi Z‌, Hajizadeh-Moghaddam A‌, Aghasi M‌, Esmaeili A‌ H. Neuroprotective effects of voluntary exercise and hydro alcoholic extraction of Eriobotrya Japonica on dopamine and tyrosine hydroxylase in the striatum of Parkinsonian rats. Koomesh. 2013; 15‌(1): 31-38. (In Persian).
10. Fallah Mohammadi Z, Mohammadi R, Aslani J. Pretreatment effects of Eriobotrya Japonica extraction on malondialdehyde (MDA), brain-derived neurotrophic factor (BDNF) and superoxide dismutase (SOD) levels in Hippocampus of rats with Parkinson's disease induced by 6-Hydroxydopamine following 12 weeks of voluntary exercise. Journal of Isfahan Medicine Scholar. 2014; 32(274): 120-30. (In Persian).
11. Al-Jarrah M‌. Exercise training and rehabilitation of brain in Parkinson’s disease. Clinical Medicine Research. 2013; 2(2): 11-17.
12. Yasuhara T, Shingo T, Date I. The potential role of vascular endothelial growth factor in the central nervous system. Rev Neurosci. 2004; 15(4): 293-307.
13. Yasuhara T, Hara K, Maki M, Matsukawa N, Fujino H, Date I, et al. Lack of exercise, via hind limb suspension, impedes endogenous neurogenesis. Neuroscience. 2007; 149(2): 182–‌91.
14. Haji Ghasem Kashani M‌, Tiraihi T‌, Ghorbanian M‌ T‌, Abrari K‌. In vitro expression of BDNF, GDNF, NGF, NT3 and NT4/5 genes in selegiline induced bone marrow stromal cells. Yakhteh Medical Journal. 2010; 11(4): 400-‌7. (In Persian).
15. Capitelli C S, Lopes C S, Alves A C, Barbiero J, Oliveira L F, Silva V J, 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. International Journal of Medical Sciences. 2014; 11(10): 1049-‌64.
16. Gibson A S J, Gao G D, McDonagh K, Shen S. Progress on stem cell research towards the treatment of Parkinson’s disease. Stem Cell Research & Therapy. 2012; 3(11): 1-10.
17. Radak Z, Kumagai Sh, Taylor A W, Naito H, Goto S. Effects of exercise on brain function: Role of free radicals. ‌Appl Physiol Nutr Metab. 2007; 32(5): 942-‌6.
18. Mabandla M V, Russell V A. Voluntary exercise reduces the neurotoxic effects of 6-hydroxydopamine in maternally separated rats. Behavioral Brain Research. 2010; 211(1): 16-22.‏
19. Valero MC, Heather DH, Jianming L, Kai Z, Marni DB. Eccentric exercise facilitates mesenchymal stem cell appearance in skeletal muscle. Plos One. 2012; 7(1): 1-11.
20. Fathi F, Altiraihi T, Mowla S J, Movahedin M. Transplantation of retinoic acid treated murine embryonic stem cells & behavioral deficit in Parkinsonian rats. Indian J Med Res. 2010; 131(5): 536-‌44. (In Persian).
21.Tajiri N, Yasuhara T, Shingo T, Kondo A, Yuan W, Kadota T, et al. Exercise exerts neuroprotective effects on Parkinson's disease model of rats. Brain Research. 2010; 13(10): 200-‌7. (In Persian).
22. Landers M R, Kinney J W, Breukelen F V. Forced exercise before or after induction of 6-OHDA-mediated nigrostriatal insult does not mitigate behavioral asymmetry in a hemiparkinsonian rat model. Brain Research. 2014; 1543(3) 263-‌70.
23. Nezhadi A, Ghazi F, Bakhtiari M, Ataiy Z, Mehdizadeh M. Differentiation of bone marrow stromal cells in dopaminergic cells in rat model of Parkinson’s disease. JAUMS. 2011; 8(4): 235-‌43. (In Persian).
24. Allbutt H N, Henderson J M. Use of the narrow beam test in the rat, 6-hydroxydopamine model of Parkinson’s disease. Journal of Neuroscience Methods. 2007; 159(1): 195–202.
25. Al-Jarrah M, Jamous M, Al-Zailaey K O, Bweir S. Endurance exercise training promotes angiogenesis in the brain of chronic/ progressive mouse model of Parkinson's disease. Neuro Rehabilitation. 2010; 26(4): 369-73.
26. Adami R‌, Scesa G‌, Bottai D‌. Stem cell transplantation in neurological diseases: Improving effectiveness in animal odels. Cell and Developmental Biology. 2014; 2(17): 1-28.
27. Wahl P, Brixius K, Bloch W. Exercise-induced stem cell activation and its implication for cardiovascular and skeletal muscle regeneration. Minimally Invasive Theraoy. 2008; 17(2): 91-99.
28. Polgar S, Karimi L, Morris M E. Stem cell therapy for Parkinson’s disease: Are double-blind randomized control trials the best design for quantifying therapy outcomes? J Neurol Neurophysiol. 2013; 4(5): 1-6.
29. Thomas M G, Stone L, Evill L, Ong S, Ziman M, Hool L. Bone marrow stromal cells as replacement cells for Parkinson's disease: Generation of an anatomical but not functional neuronal phenotype. Transl Res. 2011; 2(3): 45-53.
30. Nourshahi M, Taheri Chadorneshin H, Ranjbar K. The stimulus of angiogenesis during exercise and physical activity. Quarterly of the Horizon of Medical Sciences. 2013; 18(5): 286-‌96. (In Persian).
31. Villar-Cheda B, Sousa-Ribeiro D, Rodriguez-Pallares J, Rodriguez-Perez A I, Guerra M J, Labandeira-Garcia J L. Aging and sedentarism decrease vascularization and VEGF levels in the rat substantia nigra. Implications for Parkinson's disease. Journal of Cerebral Blood Flow & Metabolism. 2008; 29(2): 230-‌4.
32. Cadet J, Last R, Osticv K, Rezedborski P, Lewis V J. Long term behavioral and biochemical effect of 6-OHDA injection in rat caudate putamen. Brain Res Ball. 1991; 26(2): 707-‌13.
33. Murray D K, Sacheli M A, Eng J J, Stoessl A J. The effects of exercise on cognition in Parkinson’s disease: A systematic review. Translational Neurodegeneration. 2014; 3(5): 1-13.