Protective effects of erythropoietin against cuprizone-induced oxidative stress and demyelination in the mouse corpus callosum

Document Type : Original Article

Authors

1 Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Medical Nanotechnologies, School of Advanced Technologies, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Anatomical Sciences, Medical Sciences Faculty, Tarbiat Modares University, Tehran, Iran

4 Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran

5 Faculty of Medicine, Institute of Neuroanatomy, RWth Aachen University, Aachen, Germany

Abstract

Objective(s): Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of multiple sclerosis. The aim of the present work is to investigate the protective effects of erythropoietin against cuprizone-induced oxidative stress.
Materials and Methods: Adult male C57BL/6J mice were fed a chow containing 0.2 % cuprizone for 6 weeks. After 3 weeks, mice were simultaneously treated with erythropoietin (5,000 IU/ kg body weight) by daily intraperitoneal injections.
Results: Our results showed that cuprizone induced oxidative stress accompanied with down-regulation of subunits of the respiratory chain complex and demyelination of corpus callosum. Erythropoietin antagonized these effects. Biochemical analysis showed that oxidative stress induced by cuprizone was regulated by erythropoietin. Similarly, erythropoietin induced the expression of subunits of the respiratory chain complex over normal control values reflecting a mechanism to compensate cuprizone-mediated down-regulation of these genes.
Conclusion: The data implicate that erythropoietin abolishes destructive cuprizone effects in the corpus callosum by decreasing oxidative stress and restoring mitochondrial respiratory enzyme activity.

Keywords

References

1.Xia Z, White CC, Owen EK, Von Korff A, Clarkson SR, McCabe CA, et al. Genes and Environment in Multiple Sclerosis project: A platform to investigate multiple sclerosis risk. Ann Neurol  2016; 79:178-189.
2.Vakilzadeh G, Khodagholi F, Ghadiri T, Darvishi M, Ghaemi A, Noorbakhsh F, et al. Protective effect of a cAMP analogue on behavioral deficits and neuropatho-logical changes in cuprizone model of demyelination. Mol Neurobiol 2015; 52:130-141.
3.Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodri-guez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelina-tion. Ann Neurol 2000; 47:707-717.
4.Praet J, Guglielmetti C, Berneman Z, Van der Linden A, Ponsaerts P. Cellular and molecular neuropathology of the cuprizone mouse model: clinical relevance for multiple sclerosis. Neurosci Biobehav Rev 2014; 47:485-505.
5.Haider L. Inflammation, iron, energy failure, and oxidative stress in the pathogenesis of multiple sclerosis. Oxid Med Cell Longev 2015; 2015:725370.
6.Dadhania VP, Trivedi PP, Vikram A, Tripathi DN. Nutraceuticals against Neurodegeneration: A Mechanistic Insight. Curr Neuropharmacol 2016; 14:627-640.
7.Kasote DM, Hegde MV, Katyare SS. Mitochondrial dysfunction in psychiatric and neurological diseases: cause(s), consequence(s), and implications of antioxidant therapy. Biofactors 2013; 39:392-406.
8.Sinha K, Das J, Pal PB, Sil PC. Oxidative stress: the mitochondria dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol 2013; 87:1157-1180.
9.Carvalho AN, Lim JL, Nijland PG, Witte ME, Van Horssen J. Glutathione in multiple sclerosis: more than just an antioxidant? Mult Scler 2014; 20:1425-1431.
10.Liu J, Tian D, Murugan M, Eyo UB, Dreyfus CF, Wang W, et al. Microglial Hv1 proton channel promotes cuprizone-induced demyelination through oxidative damage. J Neurochem 2015; 135:347-356.
11.Kaneko N, Kako E, Sawamoto K. Enhancement of ventricular-subventricular zone-derived neurogenesis and oligodendrogenesis by erythropoietin and its derivatives. Front Cell Neurosci 2013; 7:235.
12.Csete M, Rodriguez L, Wilcox M, Chadalavada S. Erythro-poietin receptor is expressed on adult rat dopaminergic neurons and erythropoietin is neurotrophic in cultured dopaminergic neuroblasts. Neurosci Lett 2004; 359:124-126.
13.Yuan R, Maeda Y, Li W, Lu W, Cook S, Dowling P. Erythropoietin: a potent inducer of peripheral immuno/-inflammatory modulation in autoimmune EAE. PLoS One 2008; 3:e1924.
14.Najmi Varzaneh F, Najmi Varzaneh F, Azimi AR, Rezaei N, Sahraian MA. Efficacy of combination therapy with erythropoietin and methylprednisolone in clinical recovery of severe relapse in multiple sclerosis. Acta Neurol Belg 2014; 114:273-278.
15.Cervellini I, Ghezzi P, Mengozzi M. Therapeutic efficacy of erythropoietin in experimental autoimmune encephalomyelitis in mice, a model of multiple sclerosis. Methods Mol Biol 2013; 982:163-173.
16.Cervellini I, Annenkov A, Brenton T, Chernajovsky Y, Ghezzi P, Mengozzi M. Erythropoietin (EPO) increases myelin gene expression in CG4 oligodendrocytecells through the classical EPO receptor. Mol Med 2013; 19:223-229.
17.Hagemeyer N, Boretius S, Ott C, Von Streitberg A, Welpinghus H, Sperling S, et al. Erythropoietin attenuates neurological and histological consequences of toxic  demyelination in mice. Mol Med 2012; 18:628-635.
18.Kashani IR, Rajabi Z, Akbari M, Hassanzadeh G, Mohseni A, Eramsadati MK, et al. Protective effects of melatonin against mitochondrial injury in a mouse model of multiple sclerosis. Exp Brain Res 2014; 232:2835-2846.
19. Suneetha A, Raja Rajeswari K. Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review. J Chromatogr B Analyt Technol Biomed Life Sci 2016; S1570-0232:30090-30093.
20. Lassmann H. What drives disease in multiple sclerosis: Inflammation or neurodegeneration? Clin Exp Neuroimmu-nol 2010; 1:2-11.
21.Lassmann H. Pathology and disease mechanisms in different stages of multiple sclerosis. J Neurol Sci 2013; 333:1-4.
22.Torkildsen Ø, Brunborg LA, Thorsen F, Mørk SJ, Stangel M, Myhr KM, et al Effects of dietary intervention on MRI activity, de- and remyelination in the cuprizone model for demyelination. Exp Neurol 2009; 215:160-166.
23.Lassmann H, Bradl M. Multiple sclerosis: experimental models and reality. Acta Neuropathol 2016; [Epub ahead of print] Review.
24. Tanaka T, Murakami K, Bando Y, Yoshida S. Minocycline reduces remyelination by suppressing ciliary neurotro-phic factor expression after cuprizone induced demyelina-tion. J Neurochem 2013; 127:259-270.
25.Acs P, Kipp M, Norkute A, Johann S, Clarner T, Braun A, et al. 17beta estradiol  and  progesterone  prevent cuprizone  provoked  demyelination  of corpus callosum  in male mice. Glia 2009; 57:807-814.
26.Ljubisavljevic S, Stojanovic I. Neuroinflammation and demyelination from the point of nitrosative stress as 
a new target for neuroprotection. Rev Neurosci 2015; 26: 49-73.
27.Kostic M, Zivkovic N, Stojanovic I. Multiple sclerosis and glutamate excitotoxicity. Rev Neurosci 2013; 24:71-88.
28.Akisu M, Tuzun S, Arslanoglu S, Yalaz M, Kultursay N. Effect of recombinant human erythropoietin administra-tion on lipid peroxidation and antioxidant enzyme(s) activities in preterm infants. Acta Med Okayama 2001; 55:357-362.
29.Bailey DM, Lundby C, Berg RM, Taudorf S, Rahmouni H, Gutowski M, et al. On the antioxidant properties of erythropoietin and its association with the oxidative-nitrosative stress response to hypoxia in humans. Acta Physiol (Oxf) 2014; 212:175-187.
30.Yildirim E, Ozisik K, Solaroglu I, Kaptanoglu E, Beskonakli E, Sargon MF, et al. Protective  effect of  erythropoietin  on type  II  pneumocyte  cells  after traumatic brain  injury  in rats. J Trauma 2005; 58:1252-1258.
31.Akdemir Ozisik P, Oruckaptan H, Ozdemir Geyik P, Misirlioglu M, Sargon MF, Kilinc K, et al. Effect of erythropoietin on brain tissue after experimental head trauma in rats. Surg Neurol 2007; 68:547-555.
32.Sims B, Clarke M, Njah W, Hopkins ES, Sontheimer H. Erythropoietin induced  neuroprotection  requires cysteine glutamate  exchanger activity. Brain Res 2010; 1321:88-95.
33.Hametner S, Wimmer I, Haider L, Pfeifenbring S, Brück W, Lassmann H. Iron and neurodegeneration in the multiple sclerosis brain. Ann Neurol 2013; 74:848-861.
34.Rawji KS, Yong VW. The benefits and detriments of macrophages/microglia in models of multiplesclerosis. Clin Dev Immunol 2013; 2013:948976.
35.Plenge U, Belhage B, Guadalupe-Grau A, Andersen PR, Lundby C, Dela F, et al. Erythropoietin treatment enhances muscle mitochondrial capacity in humans. Front Physiol 2012; 3:50.
Iranian Journal of Basic Medical Sciences
Volume 20, Issue 8
August 2017
Pages 886-893

Files

Share

How to cite

Statistics