[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit ::
Main Menu
Journal Information::
Articles Archive::
Guide for Authors::
For Reviewers::
Ethical Statements::
Site Facilities::
Contact us::
Search in website

Advanced Search
Receive site information
Enter your Email in the following box to receive the site news and information.
Copyright Policies




Open Access Policy

This journal provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

:: Volume 11, Issue 4 (Autumn 2023) ::
Shefaye Khatam 2023, 11(4): 1-11 Back to browse issues page
The Effect of Aerobic Training and Resveratrol on Ferroptosis in a Rat Model of Alzheimer's Disease
Shiva Habibi , Ahmad Abdi * , Saeid Saeid Fazelifar
Department of Exercise Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran , a.abdi58@gmail.com
Abstract:   (353 Views)
Introduction: Ferroptosis is a type of iron-dependent cell death that has been identified in the brains of patients with Alzheimer's disease (AD). Exercise and resveratrol (RSV) can delay neurodegenerative diseases, especially AD. The present study aimed to investigate the effect of aerobic training and RSV on hippocampal ferroptosis in a rat model of AD. Materials and Methods: In this experimental study, 35 male Wistar rats were divided into 5 groups: Control (CTRL), AD, AD-Training (ADT), AD-RSV (ADRSV), and AD-Training-RSV (ADTRSV). The ADRSV and ADTRSV groups received 20 mg/Kg of RSV orally during the intervention period. An aerobic exercise program including running on a treadmill with a speed of 6-18 meters per minute, was performed 5 days a week for eight weeks. Iron and GSH levels were measured by ELISA and gene expression by Real time-PCR method. Results: AD induction caused a significant increase in iron level and a decrease in GSH, Gpx4, Nrf2, and HO-1 expression compared to the CTRL group. Exercise and RSV decreased iron and increased GSH, Nrf2, and HO-1 values compared to the AD group. Moreover, a significant increase was observed in the levels of GSH, Gpx4, Nrf2, and HO-1 in the ADTRSV group compared to the ADT and ADRSV groups compared to the other groups. Conclusion: AD induction was associated with an increase in ferroptosis indices, and aerobic exercise activity and RSV administration improved this process. Considering the effect of aerobic training and RSV, these two treatment methods can be used together to improve neurodegenerative diseases, such as AD.
Keywords: Exercise, Resveratrol, Ferroptosis, Alzheimer Disease
Full-Text [PDF 1181 kb]   (279 Downloads)    
Type of Study: Research --- Open Access, CC-BY-NC | Subject: Neuropharmacology
1. Weiland A, Wang Y, Wu W, Lan X, Han X, Li Q, et al. Ferroptosis and its role in diverse brain diseases. Molecular neurobiology. 2019; 56: 4880-93. [DOI:10.1007/s12035-018-1403-3]
2. Chen X, Comish PB, Tang D, Kang R. Characteristics and biomarkers of ferroptosis. Frontiers in cell and developmental biology. 2021;9:637162. [DOI:10.3389/fcell.2021.637162]
3. Ayton S, Wang Y, Diouf I, Schneider JA, Brockman J, Morris MC, et al. Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology. Molecular psychiatry. 2020; 25(11): 2932-41. [DOI:10.1038/s41380-019-0375-7]
4. Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nature cell biology. 2014; 16(12): 1180-91. [DOI:10.1038/ncb3064]
5. Shah R, Shchepinov MS, Pratt DA. Resolving the role of lipoxygenases in the initiation and execution of ferroptosis. ACS central science. 2018; 4(3): 387-96. [DOI:10.1021/acscentsci.7b00589]
6. Liddell JR, White AR. Nexus between mitochondrial function, iron, copper and glutathione in Parkinson's disease. Neurochemistry international. 2018; 117: 126-38. [DOI:10.1016/j.neuint.2017.05.016]
7. Yamamoto M, Kensler TW, Motohashi H. The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis. Physiological reviews. 2018; 98(3): 1169-203. [DOI:10.1152/physrev.00023.2017]
8. Abdalkader M, Lampinen R, Kanninen KM, Malm TM, Liddell JR. Targeting Nrf2 to suppress ferroptosis and mitochondrial dysfunction in neurodegeneration. Frontiers in Neuroscience. 2018; 12: 466. [DOI:10.3389/fnins.2018.00466]
9. Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S, Ingold I, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nature chemical biology. 2017; 13(1): 91-8. [DOI:10.1038/nchembio.2239]
10. Sofi F, Valecchi D, Bacci D, Abbate R, Gensini GF, Casini A, et al. Physical activity and risk of cognitive decline: a meta‐analysis of prospective studies. Journal of internal medicine. 2011; 269(1): 107-17. [DOI:10.1111/j.1365-2796.2010.02281.x]
11. Hortobágyi T, Vetrovsky T, Balbim GM, Silva NCBS, Manca A, Deriu F, et al. The impact of aerobic and resistance training intensity on markers of neuroplasticity in health and disease. Ageing Research Reviews. 2022: 101698. [DOI:10.1016/j.arr.2022.101698]
12. Liu T, Cui Y, Dong S, Kong X, Xu X, Wang Y, et al. Treadmill training reduces cerebral ischemia-reperfusion injury by inhibiting ferroptosis through activation of SLC7A11/GPX4. Oxidative Medicine and Cellular Longevity. 2022; 2022. [DOI:10.1155/2022/8693664]
13. Chen J, Zhu T, Yu D, Yan B, Zhang Y, Jin J, et al. Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and Cognitive Impairments via Suppressing STING Pathway. Molecular Neurobiology. 2023: 1-25. [DOI:10.1007/s12035-023-03379-8]
14. Bhat KP, Kosmeder JW, Pezzuto JM. Biological effects of resveratrol. Antioxidants and redox signaling. 2001;3(6):1041-64. [DOI:10.1089/152308601317203567]
15. Lin Y-T, Wu Y-C, Sun G-C, Ho C-Y, Wong T-Y, Lin C-H, et al. Effect of Resveratrol on Reactive Oxygen Species-Induced Cognitive Impairment in Rats with Angiotensin II-Ind uced Early Alzheimer's Disease. Journal of clinical medicine. 2018; 7(10): 329. [DOI:10.3390/jcm7100329]
16. Tellone E, Galtieri A, Russo A, Giardina B, Ficarra S. Resveratrol: a focus on several neurodegenerative diseases. Oxidative medicine and cellular longevity. 2015; 2015. [DOI:10.1155/2015/392169]
17. Zhang X, Jiang L, Chen H, Wei S, Yao K, Sun X, et al. Resveratrol protected acrolein-induced ferroptosis and insulin secretion dysfunction via ER-stress-related PERK pathway in MIN6 cells. Toxicology. 2022; 465: 153048. [DOI:10.1016/j.tox.2021.153048]
18. Yammine A, Zarrouk A, Nury T, Vejux A, Latruffe N, Vervandier-Fasseur D, et al. Prevention by dietary polyphenols (resveratrol, quercetin, apigenin) against 7-ketocholesterol-induced oxiapoptophagy in neuronal N2a cells: Potential interest for the treatment of neurodegenerative and age-related diseases. Cells. 2020; 9(11): 2346. [DOI:10.3390/cells9112346]
19. Svensson M, Rosvall P, Boza-Serrano A, Andersson E, Lexell J, Deierborg T. Forced treadmill exercise can induce stress and increase neuronal damage in a mouse model of global cerebral ischemia. Neurobiology of stress. 2016; 5: 8-18. [DOI:10.1016/j.ynstr.2016.09.002]
20. Shen X, Li A, Zhang Y, Dong X, Shan T, Wu Y, et al. The effect of different intensities of treadmill exercise on cognitive function deficit following a severe controlled cortical impact in rats. International journal of molecular sciences. 2013; 14(11): 21598-612. [DOI:10.3390/ijms141121598]
21. Eslimiesfahani D, Oryan S, Khosravi M, Valizadegan F. Effect of fennel extract on the improvement of memory disorders in beta amyloid alzheimer model of male wistar rats. 2019. [DOI:10.29252/sjimu.27.1.1]
22. Wu C, Yang L, Li Y, Dong Y, Yang B, Tucker LD, et al. Effects of exercise training on anxious-depressive-like behavior in Alzheimer rat. Medicine and science in sports and exercise. 2020; 52(7): 1456. [DOI:10.1249/MSS.0000000000002294]
23. Monserrat Hernández‐Hernández E, Serrano‐García C, Antonio Vázquez‐Roque R, Díaz A, Monroy E, Rodríguez‐Moreno A, et al. Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats. Synapse. 2016; 70(5): 206-17. [DOI:10.1002/syn.21888]
24. Zhao H, Li N, Wang Q, Cheng X, Li X, Liu T. Resveratrol decreases the insoluble Aβ1-42 level in hippocampus and protects the integrity of the blood-brain barrier in AD rats. Neuroscience. 2015; 310: 641-9. [DOI:10.1016/j.neuroscience.2015.10.006]
25. Ellmann G. Quantitative determination of peptides by sulfhydryl (-SH) groups. Arch Biochem Biophys. 1959; 82(1): 70-7.
26. Bao W-D, Pang P, Zhou X-T, Hu F, Xiong W, Chen K, et al. Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer's disease. Cell Death & Differentiation. 2021; 28(5): 1548-62. [DOI:10.1038/s41418-020-00685-9]
27. Li L-B, Chai R, Zhang S, Xu S-F, Zhang Y-H, Li H-L, et al. Iron exposure and the cellular mechanisms linked to neuron degeneration in adult mice. Cells. 2019;8(2):198. [DOI:10.3390/cells8020198]
28. Ashraf A, So P-W. Spotlight on ferroptosis: iron-dependent cell death in Alzheimer's disease. Frontiers in aging neuroscience. 2020:196. [DOI:10.3389/fnagi.2020.00196]
29. Zhang G, Zhang Y, Shen Y, Wang Y, Zhao M, Sun L. The potential role of ferroptosis in Alzheimer's disease. Journal of Alzheimer's Disease. 2021;80(3):907-25. [DOI:10.3233/JAD-201369]
30. Wang C, Chen S, Guo H, Jiang H, Liu H, Fu H, et al. Forsythoside a mitigates alzheimer's-like pathology by inhibiting ferroptosis-mediated neuroinflammation via Nrf2/GPX4 axis activation. International Journal of Biological Sciences. 2022;18(5):2075. [DOI:10.7150/ijbs.69714]
31. Panes JD, Godoy PA, Silva-Grecchi T, Celis MT, Ramirez-Molina O, Gavilan J, et al. Changes in PGC‐1α/SIRT1 signaling impact on mitochondrial homeostasis in amyloid-beta peptide toxicity model. Frontiers in pharmacology. 2020;11:709. [DOI:10.3389/fphar.2020.00709]
32. Yan H-f, Zou T, Tuo Q-z, Xu S, Li H, Belaidi AA, et al. Ferroptosis: mechanisms and links with diseases. Signal transduction and targeted therapy. 2021;6(1):49. [DOI:10.1038/s41392-020-00428-9]
33. Qu Z, Sun J, Zhang W, Yu J, Zhuang C. Transcription factor NRF2 as a promising therapeutic target for Alzheimer's disease. Free Radical Biology and Medicine. 2020;159:87-102. [DOI:10.1016/j.freeradbiomed.2020.06.028]
34. Aboudeya HM, Michel TN, Attia MM, Abdou AS. Neuroprotective effect of Exercise on Alzheimer's disease in rats: Role of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2). Bulletin of Egyptian Society for Physiological Sciences. 2021;41(3):331-43. [DOI:10.21608/besps.2020.44355.1074]
35. Zare M, Nayebifar S, Aminizadeh S, Vahidian-Rezazadeh M. The Effects of Six Weeks of Endurance Training and CGRP Inhibition on Nrf2 and AKT Expression in the Hippocampal Tissue of Male Wistar Rats. Mediators of Inflammation. 2022;2022. [DOI:10.1155/2022/1610293]
36. Xia B, Liu H, Xie J, Wu R, Li Y. Akt enhances nerve growth factor-induced axon growth via activating the Nrf2/ARE pathway. International journal of molecular medicine. 2015;36(5):1426-32. [DOI:10.3892/ijmm.2015.2329]
37. Abshenas R, Artimani T, Amiri I, Shahidi S, Najafi R, Soleimani Asl S. Effects of treadmill exercise and preconditioned bone marrow- derived mesenchymal stem cells transplantation on Aβ-induced neurotoxicity in male rats. Koomesh journal. 1399;22(2):325-33. [DOI:10.29252/koomesh.22.2.325]
38. Hirata Y, Tsunekawa Y, Takahashi M, Oh-Hashi K, Kawaguchi K, Hayazaki M, et al. Identification of novel neuroprotective N, N-dimethylaniline derivatives that prevent oxytosis/ferroptosis and localize to late endosomes and lysosomes. Free Radical Biology and Medicine. 2021;174:225-35. [DOI:10.1016/j.freeradbiomed.2021.08.015]
39. Kato K, Takahashi M, Oh-Hashi K, Ando K, Hirata Y. Quercetin and resveratrol inhibit ferroptosis independently of Nrf2-ARE activation in mouse hippocampal HT22 cells. Food and Chemical Toxicology. 2023;172:113586. [DOI:10.1016/j.fct.2022.113586]
40. Li Y, Huang Z, Pan S, Feng Y, He H, Cheng S, et al. Resveratrol Alleviates Diabetic Periodontitis-Induced Alveolar Osteocyte Ferroptosis Possibly via Regulation of SLC7A11/GPX4. Nutrients. 2023;15(9):2115. [DOI:10.3390/nu15092115]
41. Ni C, Ye Q, Mi X, Jiao D, Zhang S, Cheng R, et al. Resveratrol inhibits ferroptosis via activating NRF2/GPX4 pathway in mice with spinal cord injury. Microscopy Research and Technique. 2023. [DOI:10.1002/jemt.24335]
42. Yan P, Li Z, Xiong J, Geng Z, Wei W, Zhang Y, et al. LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity. Cell Reports. 2021;37(8). [DOI:10.1016/j.celrep.2021.110038]
43. Jiang L, Kon N, Li T, Wang S-J, Su T, Hibshoosh H, et al. Ferroptosis as a p53-mediated activity during tumour suppression. Nature. 2015;520(7545):57-62. [DOI:10.1038/nature14344]
44. Wei Z, Shaohuan Q, Bi T, Heng Z, Chao S. Resveratrol inhibits ferroptosis and decelerates heart failure progression via Sirt1/p53 pathway activation. 2023. [DOI:10.21203/rs.3.rs-2862963/v1]
45. Liao Z-Y, Chen J-L, Xiao M-H, Sun Y, Zhao Y-X, Pu D, et al. The effect of exercise, resveratrol or their combination on Sarcopenia in aged rats via regulation of AMPK/Sirt1 pathway. Experimental Gerontology. 2017;98:177-83. [DOI:10.1016/j.exger.2017.08.032]

XML   Persian Abstract   Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Habibi S, Abdi A, Saeid Fazelifar S. The Effect of Aerobic Training and Resveratrol on Ferroptosis in a Rat Model of Alzheimer's Disease. Shefaye Khatam 2023; 11 (4) :1-11
URL: http://shefayekhatam.ir/article-1-2429-en.html

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 11, Issue 4 (Autumn 2023) Back to browse issues page
مجله علوم اعصاب شفای خاتم The Neuroscience Journal of Shefaye Khatam
Persian site map - English site map - Created in 0.05 seconds with 45 queries by YEKTAWEB 4652