Exercise Preconditioning Reduces Spatial Memory Disorder Induced by Cerebral Ischemia Via Increasing the Expression of Neurotrophins In Rat Hippocampus

Document Type : Research Paper

Authors
Nabi Shamsaei 1
Hamid Rajabi 2
Nahid Aboutaleb 3
1 Assistant Professor of Exercise Physiology, Ilam University
2 Professor of Exercise Physiology, Kharazmi University
3 Associated Professor of Medical Physiology, Iran University of Medical Sciences
10.22089/spj.2017.951
Abstract
The aim of this study was the study of effect of exercise preconditioning on spatial memory disorders and expression of BDNF and NGF proteins in the CA1 area of hippocampus following cerebral ischemia-reperfusion in male rats. 21 male Wistar rats were randomly selected and allocated into three groups (sham, ischemia and exercise + ischemia). The rats in exercise group were trained to run on the treadmill 5 days in a week for 4 weeks. Ischemia induced by occlusion both common carotid arteries for 20 minutes. Spatial memory performances of rats were evaluated by the Morris water maze. The level of proteins expression was determined by immunohistochemically staining. Exercise preconditioning significantly decreased the time and distance traversed to reach the platform in Morris water maze. Also, pre-ischemic exercise significantly increased the expression of BDNF and NGF proteins in the CA1 area of hippocampus compared to the ischemia group. Exercise preconditioning, probably via up-regulation of neurotrophic factors, could have neuroprotective effects against brain ischemia-reperfusion-induced injuries and improve short-term memory impairments induced by cerebral ischemia.
Keywords
Ischemia
Exercise
Hippocampus
Spatial Memory
Neurotrophin

Main Subjects

  1. Dirnagl U, Iadecola C, Moskowitz M A. Pathobiology of ischaemic stroke: An integrated view. Trend Neurosci. 1999; 22(9): 391-7.
  2. Siesj B K. Pathophysiology and treatment of focal cerebral ischemia. J Neurosurg. 1992; 77(2): 169-84.
  3. Gheibi S‌, Khaksari M‌, Kalalian-Moghaddam H‌, Majd Z‌, Zare Mehrjerdi F‌, Aboutaleb N‌. The effect of NaHS on behavioral neurological dysfunction following focal cerebral ischemia in Rats. J Knowledge Health. 2014; 9(1);       68-73. (In Persian).
  4. Kirino T, Tamura A, Sano K. Selective vulnerability of the hippocampus to ischemia reversible and irreversible types of ischemic cell damage. Prog Brain Res. 1985; 63(1): 39-58.
  5. Netto C, Hodges H, Sinden J, Le Peillet E, Kershaw T, Sowinski P, et al. Effects of fetal hippocampal field grafts on ischaemic-induced deficits in spatial navigation in the water maze. Neuroscience. 1993; 54(1): 69-92.
  6. Wang Y, Qin Z H. Molecular and cellular mechanisms of excitotoxic neuronal death. Apoptosis. 2012; 15(11): 1382-402.
  7. Albasser M M, Amin E, Lin T C E, Iordanova M D, Aggleton J P. Evidence that the Rat hippocampus has contrasting roles in object recognition memory and object recency memory. Behav Neurosci. 2012; 126(5): 659-69.
  8. Deister C, Schmidt C E. Optimizing neurotrophic factor combinations for neurite outgrowth. J Neural Eng. 2006; 3(2): 172-9.
  9. Dornbos III D, Ding Y. Mechanisms of neuroprotection underlying physical exercise in ischemia-reperfusion injury. First ed. Rijeka, Croatia: Intech Open Access Publisher; 2012. P. 299-326.
  10. Kochanski R, Dornbos III D, Ding Y. Neuroprotection and physical preconditioning: Exercise, hypothermia, and hyperthermia. First ed. New York, USA: Innate Tolerance CNS; 2013. P. 105-31.
  11. Allen S J, Dawbarn D. Clinical relevance of the neurotrophins and their receptors. Clin Sci. 2006; 110(2): 175-91.
  12. Bariohay B, Lebrun B, Moyse E, Jean A. Brain-derived neurotrophic factor plays a role as an anorexigenic factor in the dorsal vagal complex. Endocrinology. 2005; 146(12): 5612-20.
  13. Duman R S. Synaptic plasticity and mood disorders. Mol Psychiatry. 2002; 7(1): 29–34.
  14. Kokaia Z, Andsberg G, Yan Q, Lindvall O. Rapid alterations of BDNF protein levels in the Rat brain after focal ischemia: Evidence for increased synthesis and anterograde axonal transport. Exp Neurol. 1998; 154(2): 289-301.
  15. Schäbitz W R, Steigleder T, Cooper-Kuhn C M, Schwab S, Sommer C, Schneider A, et al. Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis. Stroke. 2007; 38(7):       2165-72.
  16. Cohen-Cory S, Kidane A H, Shirkey N J, Marshak S. Brain-derived neurotrophic factor and the development of structural neuronal connectivity. Dev Neurobiol. 2010; 70(5); 271-88.
  17. Zhang P, Zhang Q, Pu H, Wu Y, Bai Y, Vosler P. Very early-initiated physical rehabilitation protects against ischemic brain injury. Front Biosci (Elite Ed). 2011; 4(1); 2476-89.
  18. Shamsaei N‌, Rajabi H‌, Aboutaleb N‌, Nikbakht F‌, Motamedi P‌, Khaksari M‌, et al. Effects of exercise pre-conditioning on hippocampus expression of Bcl-2 and Bax protein and apoptosis following ischemia/ reperfusion injury in male Rats. J Knowledge Health. 2015; 10(2): 24-32. (In Persian).
  19. Tahamtan M‌, Allahtavakoli M‌, Taghavi M‌ M‌, Rezazadeh H‌, Arababadi M‌, Shamsizade A‌. The effect of exercise preconditioning on tactile learning following transient cerebral ischemia in male Rats. ZUMS J. 2013; 21(84):         36-46. (In Persian).
  20. Wu A, Ying Z, Gomez-Pinilla F. Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience. 2008; 155(3): 751-‌9.
  21. Cotman C W, Berchtold N C. Exercise: A behavioral intervention to enhance brain healthand plasticity. Trends Neuroscience. 2002; 25(6): 295-301.
  22. Ding Y H, Luan X D, Li J, Rafols J A, Guthinkonda M, Diaz F G, et al. Exercise-induced overexpression of angiogenic factors and reduction of ischemia/reperfusion injury in stroke. Cur Neurovasc Res. 2004; 1(5); 411-20.
  23. Ding Y, Li J, Luan X, Ding Y H, Lai Q, Rafols J A, ‌et al. Exercise preconditioning reduces brain damage in ischemic rats that may be associated with regional angiogenesis and cellular overexpression of neurotrophin. Neuroscience. 2004; 124(3): 583-91.
  24. Duzova H, Karakoc Y, Emre M H, Dogan Z Y, Kilinc E. Effects of acute moderate and strenuous exercise bouts on IL-17 production and inflammatory response in trained rats. J Sports Sci Med. 2009; 8(2): 219-24.
  25. Kevin C, Kregel D‌ L. Resource book for the design of animal exercise protocols. 5th ed. Iowa, USA: American Physiological Society; 2006. P. 23-57.
  26. Zhang F, Wu Y, Jia J. Exercise preconditioning and brain ischemic tolerance. Neuroscience. 2011; 177(1): 170-6.
  27. Zhang F, Jia J, Wu Y, Hu Y, Wang Y. The effect of treadmill training pre-exercise on glutamate receptor expression in rats after cerebral ischemia. Int J Mol Sci. 2010‌; 11(7): 2658-69.
  28. Erfani S, Khaksari M, Oryan SH, Shamsaei N, Aboutaleb N, Nikbakht F. Nampt/ PBEF/ Visfatin exerts neuroprotective effects against ischemia/ reperfusion injury via modulation of Bax/ Bcl-2 ratio and prevention of Caspase-3 activation. J Mol Neurosci. 2015; 56(1): 237-43. (In Persian).
  29. Aboutaleb N, Kalalian Moghaddam H, Eftekhari S, Shahbazi A, Abbaspour H, Khaksari M. Apelin-13 inhibits apoptosis of cortical neurons following brain ischemic reperfusion injury in a transient model of focal cerebral ischemia. Int J Pept Res Therap. 2014; 20(2): 127-32.
  30. Paxinos G, Watson C. The Rat brain in stereotaxic coordinates. 6th ed. San Diego, USA: Academic Press; 2006. P. 13-153.
  31. Gheibi S, Aboutaleb N, Khaksari M, Kalalian Moghaddam H, Vakili A, Asadi Y, et al. Hydrogen sulfide protects the brain against ischemic reperfusion injury in a transient model of focal cerebral ischemia. J Mol Neurosci. 2014; 54(2): 264-70. (In Persian).
  32. Wang J Y, Shen J, Gao Q, Ye Z G, Yang S Y, Liang H W, et al. Ischemic postconditioning protects against global cerebral ischemia/ reperfusion-induced injury in rats. Stroke. 2008; 39(3): 983-90.
  33. Liebelt B, Papapetrou P, Ali A, Guo M, Ji X, Peng C, et al. Exercise preconditioning reduces neuronal apoptosis in stroke by up-regulation heat shock protein-70 (heat shock protein-72) and extracellular-signal-regulatedkinase1/2. Neuroscience. 2010; 166(4): 1091-100.
  34. Ang E T, Wong P T, Moochhala S, Ng Y K. Neuroprotection associated with running: Is it a result of increased endogenous neurotrophic factors? Neuroscience. 2003; 118(2): 335-45.
  35. Berchtold N C, Chinn G, Chou M, Kesslak J P, Cotman C W. Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus. Neuroscience. 2005; 133(3): 853-61.
  36. Cechetti F, Fochesatto C, Scopel D, Nardin P, Gonçalves C A, Netto C A, et al. Effect of a neuroprotective exercise protocol on oxidative state and BDNF levels in the rat hippocampus. Brain Res. 2008; 1188(1): 182-8.
  37. Hajizade Moghadam A, Fallah Mohammadi Z, Sheykh P, Mirzaee S. Effect of voluntary exercise on a running wheel and brain-derived neurotrophic factor levels Allium Paradoxium extracts in alloxan-induced diabetic Rat hippocampus. Iranian J Diab Lipid Disord. 2012; 11(4): 350-7. (In Persian).
  38. Chan P H. Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab. 2001; 21(1): 2-14.
  39. Rahimi M‌, Asgari A‌ R‌, Khoshbaten A‌. The role of exercise preconditioning in cardioprotection against ischemia reperfusion injury. Physiol Pharmacol. 2014; 18‌(2): 122-‌43.‌ (In Persian).
  40. Faraji F‌, Ranjbar A‌, Eshrati B, Talaie A‌, Shafie N‌, Pirasteh S‌. Comparing the oxidative stress indexes of CVA patients with control group. J Arak Uni of Med Sci. 2008; 11(3): 109-16. (In Persian).
Sport Physiology
Volume 9, Issue 34 - Serial Number 34
Summer 2017
July 2017
Pages 63-78

  • Receive Date 29 November 2015
  • Revise Date 10 January 2016
  • Accept Date 13 January 2016