Volume 21, Issue 6 (12-2018)
J Arak Uni Med Sci 2018, 21(6): 34-46 |
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Sanadgol N, Maleki P. Study of the Effects of Ellagic Acid on Population and Activity of Central Nervous System Neuroglia Cells in the Cuprizone-induced Multiple Sclerosis. J Arak Uni Med Sci 2018; 21 (6) :34-46
URL: http://jams.arakmu.ac.ir/article-1-5743-en.html
URL: http://jams.arakmu.ac.ir/article-1-5743-en.html
1- Department of Biology, Faculty of Sciences, University of Zabol, Zabol, Iran. Pharmaceutical Science Research Center, Tehran University of Medical Sciences, Tehran, Iran. , n.sanadgol@uoz.ac.ir
2- Department of Biology, Faculty of Sciences, Arak University, Arak, Iran.
2- Department of Biology, Faculty of Sciences, Arak University, Arak, Iran.
Abstract: (3057 Views)
Background and Aim: Ellagic acid (EA) is a natural antioxidant with phenolic structure. In this study, we evaluate the effects of EA consumption on population and activation of neuroglia cells in the animal model of MS under oxidative stress.
Materials and Methods: Mature male mice with age of between 8 to 9 weeks were kept in the standard conditions. For model induction, animals received powder normal diet containing 0.2% Cuprizone (Cup) for six weeks. Mice were divided into eight groups containing control, control receiving three doses of EA (20, 40 and 80 mg/kg), Cup and Cup receiving three doses of EA. Finally, specific glial cell markers in the animal brain tissues were analyzed by molecular methods such as immunohistochemistry (IHC), western blotting (WB) and Real Time-PCR (RT-PCR).
Findings: IHC and WB analysis have shown that only high concentration of EA is able to reduce protein expression of GFAP (activated astrocytes marker), Mac-3 (activated microglial marker), increase protein expression of Olig-2 (oligodendrocytes precursor marker) and ultimately significant reduction on APC (mature oligodendrocytes marker)/Olig-2 ratio in comparison with Cup group. In addition, RT-PCR evaluation indicated that changes in the mRNA expression of target markers were consistent with observed changes in their protein expression and therefore, IHC and WB results were confirmed.
Conclusion: Consumption of 80 mg/kg of EA effectively decreased activation of astrocytes and microglial and so appropriates environment for migration of oligodendrocyte precursor cells to the lesion area and shifting from damage course into the repair progressions.
Materials and Methods: Mature male mice with age of between 8 to 9 weeks were kept in the standard conditions. For model induction, animals received powder normal diet containing 0.2% Cuprizone (Cup) for six weeks. Mice were divided into eight groups containing control, control receiving three doses of EA (20, 40 and 80 mg/kg), Cup and Cup receiving three doses of EA. Finally, specific glial cell markers in the animal brain tissues were analyzed by molecular methods such as immunohistochemistry (IHC), western blotting (WB) and Real Time-PCR (RT-PCR).
Findings: IHC and WB analysis have shown that only high concentration of EA is able to reduce protein expression of GFAP (activated astrocytes marker), Mac-3 (activated microglial marker), increase protein expression of Olig-2 (oligodendrocytes precursor marker) and ultimately significant reduction on APC (mature oligodendrocytes marker)/Olig-2 ratio in comparison with Cup group. In addition, RT-PCR evaluation indicated that changes in the mRNA expression of target markers were consistent with observed changes in their protein expression and therefore, IHC and WB results were confirmed.
Conclusion: Consumption of 80 mg/kg of EA effectively decreased activation of astrocytes and microglial and so appropriates environment for migration of oligodendrocyte precursor cells to the lesion area and shifting from damage course into the repair progressions.
Type of Study: Original Atricle |
Subject:
Basic Sciences
Received: 2018/04/25 | Accepted: 2018/07/25
Received: 2018/04/25 | Accepted: 2018/07/25
References
1. Sanadgol N, Zahedani SS, Sharifzadeh M, Khalseh R, Barbari GR, Abdollahi M. Recent Updates in Imperative Natural Compounds for Healthy Brain and Nerve Function: A Systematic Review of Implications for Multiple Sclerosis. Curr Drug Targets. 2017; 18(13): 1499-1517.
2. Sospedra M, Martin R. Immunology of multiple sclerosis. Annu Rev Immunol. 2005; 23: 683-747.
3. Sahraian MA, Khorramnia S, Ebrahim MM, Moinfar Z, Lotfi J, Pakdaman H. Multiple sclerosis in Iran: a demographic study of 8,000 patients and changes over time. European neurology. 2010; 64(6): 331-6.
4. Handel AE, Giovannoni G, Ebers GC, Ramagopalan SV. Environmental factors and their timing in adult-onset multiple sclerosis. Nature Reviews Neurology. 2010; 6(3): 156-66.
5. Miller DH, Leary SM. Primary-progressive multiple sclerosis. The Lancet Neurology. 2007; 6(10): 903-12.
6. Lauer K. Environmental risk factors in multiple sclerosis. Expert review of neurotherapeutics. 2010; 10(3): 421-40.
7. Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Annals of neurology. 2007; 61(6): 504-13.
8. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis results of an international survey. Neurology. 1996; 46(4): 907-11.
9. Tillery EE, Clements JN, Howard Z. What's new in multiple sclerosis? Ment Health Clin. 2018; 7(5): 213-220.
10. Sanadgol N, Golab F, Mostafaie A, Mehdizadeh M, Khalseh R, Mahmoudi M, et al. Low, but not high, dose triptolide controls neuroinflammation and improves behavioral deficits in toxic model of multiple sclerosis by dampening of NF-κB activation and acceleration of intrinsic myelin repair. Toxicol Appl Pharmacol. 2018; 342: 86-98.
11. Von Wunster B, Bailey S, Wilkins A, Marks DI, Scolding NJ, Rice CM. Advising patients seeking stem cell interventions for multiple sclerosis. Pract Neurol. 2018; 001956.
12. Sanadgol N, Golab F, Tashakkor Z, Taki N, Moradi Kouchi S, Mostafaie A, et al. Neuroprotective effects of ellagic acid on cuprizone-induced acute demyelination through limitation of microgliosis, adjustment of CXCL12/IL-17/IL-11 axis and restriction of mature oligodendrocytes apoptosis, Pharmaceutical Biology. 2017; 55:1679-1687.
13. Kettenmann, H, and Verkhratsky A. Neuroglia–living nerve glue. Fortschr. Neurol. Psychiatr. 2011; 79: 588-597.
14. Binder DK. Astrocytes: Stars of the Sacred Disease. Epilepsy Curr. 2018; 18(3): 172-179.
15. Jha MK, Jo M, Kim JH, Suk K. Microglia-Astrocyte Crosstalk: An Intimate Molecular Conversation. Neuroscientist. 2018; 1073858418783959.
16. 16. Derosa G, Maffioli P, Sahebkar A. Ellagic Acid and Its Role in Chronic Diseases. Adv Exp Med Biol. 2016; 928: 473-479.
17. Lepka K, Berndt C, Hartung HP, Aktas O. Redox Events As Modulators of Pathology and Therapy of Neuroinflammatory Diseases. Front Cell Dev Biol. 2016 ; 23: 4:63.
18. Sanadgol N, Golab F, Mostafaie A, Mehdizadeh M, Abdollahi M, Sharifzadeh M, Ravan H. Ellagic acid ameliorates cuprizone-induced acute CNS inflammation via restriction of microgliosis and down-regulation of CCL2 and CCL3 pro-inflammatory chemokines. Cell Mol Biol (Noisy-le-grand). 2016; 62(12): 24-30.
19. Sanadgol N, Golab F, Askari H, Moradi F, Ajdary M, Mehdizadeh M. Alpha-lipoic acid mitigates toxic-induced demyelination in the corpus callosum by lessening of oxidative stress and stimulation of polydendrocytes proliferation. Metab Brain Dis. 2018; 33(1): 27-37.
20. Ramroodi N, Khani M, Ganjali Z, Javan MR, Sanadgol N, Khalseh R, et al. Prophylactic Effect of BIO-1211 Small-Molecule Antagonist of VLA-4 in the EAE Mouse Model of Multiple Sclerosis. Immunol Invest. 2015; 44(7): 694-712.
21. Patel M. Targeting Oxidative Stress in Central Nervous System Disorders. Trends Pharmacol Sci. 2016; 37(9): 768-78.
22. Fan TK, Gundimeda U, Mack WJ, Gopalakrishna R. Counteraction of Nogo-A and axonal growth inhibitors by green tea polyphenols and other natural products. Neural Regen Res. 2016; 11(4): 545-6.
23. Filiano Anthony J, Gadani Sachin P, Kipnis Jonathan. Interactions of innate and adaptive immunity in brain development and function. Brain Research. 2015; 1617: 18-27.
24. Poorebrahim M, Asghari M, Abazari MF, Askari H, Sadeghi S, Taheri-Kafrani A, et al. Immunomodulatory effects of a rationally designed peptide mimetic of human IFNβ in EAE model of multiple sclerosis. Prog Neuropsychopharmacol Biol Psychiatry. 2018; 82: 49-61.
25. Lang J, Maeda Y, Bannerman P, Xu J, Horiuchi M, Pleasure D, Guo F. Adenomatous Polyposis Coli Regulates Oligodendroglial Development. J Neurosci. 2013; 33(7): 3113-3130.
26. Liu QS, Li SR, Li K, Li X, Yin X, Pang Z. Ellagic acid improves endogenous neural stem cells proliferation and neurorestoration through Wnt/β-catenin signaling in vivo and in vitro. Mol Nutr Food Res. 2017; 61(3).
27. Busto R, Serna J, Perianes-Cachero A, Quintana-Portillo R, García-Seisdedos D, Canfrán-Duque A, et al. Ellagic acid protects from myelin-associated sphingolipid loss in experimental autoimmune encephalomyelitis. Biochim Biophys Acta. 2018; 1863: 958-967.
28. Firdaus F, Faraz Zafeer M, Anis E, Ahmad M, Afzal M. Ellagic acid attenuates arsenic induced neuro-inflammation and mitochondrial dysfunction associated apoptosis. Toxicol Re. 2018; 5: 411-417.
29. Farbood Y, Sarkaki A, Dolatshahi M, Mansouri SMT, Khodadadi A. Ellagic Acid Protects the Brain Against 6-Hydroxydopamine Induced Neuroinflammation in a Rat Model of Parkinson’s Disease. Basic Clin Neurosci. 2015; 6(2): 83-89.
30. Mashhadizadeh SH, Farbood Y, Dianat M, Khodadadi A, Sarkaki.A. Therapeutic effects of ellagic acid on memory, hippocampus electrophysiology deficits, and elevated TNF-α level in brain due to experimental traumatic brain injury. Iran J Basic Med Sci. 2017; 20(4): 399-407.
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