Effects of Exercise Pre-Conditioning on Hippocampus Expression of Bcl-2 and Bax Protein and Apoptosis Following Ischemia/Reperfusion Injury in Male Rats

Authors

  • Nabi Shamsaei1 1- Dept. of Physical Education & Sports Science, School of Physical Education & Sports Science, Kharazmi University, Tehran, Iran.
  • Hamid Rajabi1
  • Nahid Aboutaleb2 2- Dept. of Physiology, Physiology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
  • Farnaz Nikbakht2
  • Pezhman Motamedi1
  • Mehdi Khaksari3 3- Dept. of Physiology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
  • Sohaila Erfani4 4- Dept. of Animal Physiology, School of Biology, Kharazmi University, Tehran, Iran.

DOI:

https://doi.org/10.22100/jkh.v10i2.672

Keywords:

Exercise, Preconditioning, Hippocampus, Ischemia, Reperfusion

Abstract

Introduction: Cerebral ischemia/reperfusion leads to loss of vulnerable neurons by apoptosis in specific brain regions specially in the hippocampus. There is some evidence indicating that the neuroprotective effects of physical activity on the brain. Therefore,the main purpose of this study was to investigate the effect of exercise pre-conditioning on apoptosis-related proteins expression in hippocampal CA1 neurons after induction of ischemia.

Methods: 21 Male rats weighing 260-300g were randomly allocated into three groups. Sham operated group, ischemia group and exercise+ischemia group. Ischemia was induced by the occlusion of both common carotid arteries (CCA) for 20 min, The rats in exercise group were trained to run on a treadmill for 4 weeks befor induction of ischemia and in sham operated group common carotid arteries do not occluded. The expression of caspase-3, Bax and Bcl-2 proteins levels were determined by immunohistochemical staining.

Results: The number of caspase-3-positive neurons in the CA1 area were significantly increased in the ischemia group, compared with the sham-operated group. Exercise pre-conditioning significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group. Moreover Bax/Bcl-2 ratio in ischemia group, significantly increased in comparision with sham-operated group. However, exercise pre-conditioning significantly attenuated the ischemia/reperfusion-induced increase in Bax/Bcl-2 ratio, as compared with the ischemia group.

Conclusion: The results indicated that exercise pre-conditioning has a neuroprotective effects on the brain ischemia. Moreover, exercise pre-conditioning may provide a useful strategy for reducing brain complications caused by hypoxic ischemia brain injury.

References

Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends in Neurosciences 1999;22:391-7.

Wang Y, Qin Z-h. Molecular and cellular mechanisms of excitotoxic neuronal death. Apoptosis 2010;15:1382-402.

Mattson M, Duan W, Pedersen W, Culmsee C. Neurodegenerative disorders and ischemic brain diseases. Apoptosis 2001;6:69-81.

Zamzami N, Susin SA, Marchetti P, Hirsch T, Gómez-Monterrey I, Castedo M, et al. Mitochondrial control of nuclear apoptosis. The Journal of Experimental Medicine 1996;183:1533-44.

Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997;91:479-89.

Benchoua A, Guégan C, Couriaud C, Hosseini H, Sampaı̈o N, Morin D, et al. Specific caspase pathways are activated in the two stages of cerebral infarction. The Journal of Neuroscience 2001;21:7127-34.

Chen J, Nagayama T, Jin K, Stetler RA, Zhu RL, Graham SH, et al. Induction of caspase-3-like protease may mediate delayed neuronal death in the hippocampus after transient cerebral ischemia. The Journal of Neuroscience 1998;18:4914-28.

Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nature reviews Molecular Cell Biology 2008;9:47-59.

Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 1997;275:1132-6.

Wattenberg B, Lithgow T. Targeting of C‐terminal (tail) ‐anchored proteins: understanding how cytoplasmic activities are anchored to intracellular membranes. Traffic 2001;2:66-71.

Antonawich FJ, Krajewski S, Reed JC, Davis JN. Bcl-x1 Bax interaction after transient global ischemia. Journal of Cerebral Blood Flow & Metabolism 1998;18:882-6.

Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science 1998;281:1322-6.

Albasser MM, Amin E, Lin T-CE, Iordanova MD, Aggleton JP. Evidence that the rat hippocampus has contrasting roles in object recognition memory and object recency memory. Behavioral Neuroscience 2012;126:659.

Kirino T, Tamura A, Sano K. Selective vulnerability of the hippocampus to ischemia-reversible and irreversible types of ischemic cell damage. Progress in Brain Research 1985;63:39-58.

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;54:69-92.

Chaudhry K, Rogers R, Guo M, Lai Q, Goel G, Liebelt B, et al. Matrix metalloproteinase-9 (MMP-9) expression and extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation in exercise-reduced neuronal apoptosis after stroke. Neuroscience Letters 2010;474:109-14.

Ding Y-H, Ding Y, Li J, Bessert DA, Rafols JA. Exercise pre-conditioning strengthens brain microvascular integrity in a rat stroke model. Neurological Research 2006;28:184-9.

Zhang P, Zhang Q, Pu H, Wu Y, Bai Y, Vosler P, et al. Very early-initiated physical rehabilitation protects against ischemic brain injury. Frontiers in Bioscience (Elite edition) 2011;4:2476-89.

Sharifi ZN, Abolhassani F, Hassanzadeh G, Zarrindast MR, Movassaghi S. Neuroprotective treatment with fk506 reduces hippocampal damage and prevents learning and memory deficits after transient global ischemia in rat. Archives of Neuroscience 2013;1:35-40.

Aboutaleb N, Kalalianmoghaddam 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. International Journal of Peptide Research and Therapeutics 2014;20:127-32.

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. Journal of Molecular Neuroscience 2014:1-7.

Zwagerman N, Plumlee C, Guthikonda M, Ding Y. Toll-like receptor-4 and cytokine cascade in stroke after exercise. Neurological Research 2010;32:123-6.

Liebelt B, Papapetrou P, Ali A, Guo M, Ji X, Peng C, et al. Exercise preconditioning reduces neuronal apoptosis in stroke by up-regulating heat shock protein-70 (heat shock protein-72) and extracellular-signal-regulated-kinase 1/2. Neuroscience 2010;166:1091-100.

Zwagerman N, Sprague S, Davis MD, Daniels B, Goel G, Ding Y. Pre-ischemic exercise preserves cerebral blood flow during reperfusion in stroke. Neurological Research 2010;32:523-9.

Jia J, Hu Y-S, Wu Y, Liu G, Yu H-X, Zheng Q-P, et al. Pre-ischemic treadmill training affects glutamate and gamma aminobutyric acid levels in the striatal dialysate of a rat model of cerebral ischemia. Life Sciences 2009;84:505-11.

Khaksari M, Aboutaleb N, Nasirinezhad F, Vakili A, Madjd Z. Apelin-13 protects the brain against ischemic reperfusion injury and cerebral edema in a transient model of focal cerebral ischemia. Journal of Molecular Neuroscience 2012;48:201-8.

Fiore R, Bayer V, Pelech S, Posada J, Cooper J, Baraban J. p42 mitogen-activated protein kinase in brain: prominent localization in neuronal cell bodies and dendrites. Neuroscience 1993;55:463-72.

Sharony R, Pintucci G, Saunders PC, Grossi EA, Baumann FG, Galloway AC, et al. Matrix metalloproteinase expression in vein grafts: role of inflammatory mediators and extracellular signal-regulated kinases-1 and-2. American Journal of Physiology-Heart and Circulatory Physiology 2006;290:H1651-H9.

Cavanaugh JE. Role of extracellular signal regulated kinase 5 in neuronal survival. European Journal of Biochemistry 2004;271:2056-9.

Hetman M, Gozdz A. Role of extracellular signal regulated kinases 1 and 2 in neuronal survival. European Journal of Biochemistry 2004;271:2050-5.

Jones NM, Bergeron M. Hypoxia‐induced ischemic tolerance in neonatal rat brain involves enhanced ERK1/2 signaling. Journal of Neurochemistry 2004;89:157-67.

Shamloo M, Wieloch T. Changes in protein tyrosine phosphorylation in the rat brain after cerebral ischemia in a model of ischemic tolerance. Journal of Cerebral Blood Flow & Metabolism 1999;19:173-83.

Chan PH. Reactive oxygen radicals in signaling and damage in the ischemic brain. Journal of Cerebral Blood Flow & Metabolism 2001;21:2-14.

Oliver CN, Starke-Reed PE, Stadtman ER, Liu GJ, Carney JM, Floyd RA. Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proceedings of the National Academy of Sciences 1990;87:5144.

Ji LL. Antioxidants and oxidative stress in exercise. Experimental Biology and Medicine 1999;222:283-92.

Hoffman-Goetz L, Spagnuolo P. Effect of repeated exercise stress on caspase 3, Bcl-2, HSP 70 and CuZn-SOD protein expression in mouse intestinal lymphocytes. Journal of Neuroimmunology 2007;187:94-101.

Botchkina GI, Meistrell 3rd M, Botchkina IL, Tracey KJ. Expression of TNF and TNF receptors (p55 and p75) in the rat brain after focal cerebral ischemia. Molecular Medicine 1997;3:765.

Sairanen T, Lindsberg P, Brenner M, Carpen O, Sirén A-L. Differential cellular expression of tumor necrosis factor-α and Type I tumor necrosis factor receptor after transient global forebrain ischemia. Journal of the Neurological Sciences 2001;186:87-99.

Bruce AJ, Boling W, Kindy MS, Peschon J, Kraemer PJ, Carpenter MK, et al. Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Nature Medicine 1996;2:788-94.

Wang R-Y, Yang Y-R, Yu S-M. Protective effects of treadmill training on infarction in rats. Brain Research 2001;922:140-3.

Reyes Jr R, Wu Y, Lai Q, Mrizek M, Berger J, Jimenez DF, et al. Early inflammatory response in rat brain after peripheral thermal injury. Neuroscience Letters 2006;407:11-5.

Published

2015-03-17

Issue

Section

Original Article(s)

How to Cite

Effects of Exercise Pre-Conditioning on Hippocampus Expression of Bcl-2 and Bax Protein and Apoptosis Following Ischemia/Reperfusion Injury in Male Rats. (2015). Knowledge and Health in Basic Medical Sciences, 10(2), Page:24-32. https://doi.org/10.22100/jkh.v10i2.672

Most read articles by the same author(s)

<< < 52 53 54 55 56 57 58 59 60 61 > >>