نقش هم افزایی تمرین هوازی و مصرف رزوراترول بر مسیر بیوژنز میتوکندری هیپوکامپ موش‌های مبتلا به آلزایمر

نوع مقاله : مقاله پژوهشی

نویسندگان

گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران

10.22070/daneshmed.2024.19127.1494

چکیده

مقدمه و هدف: پاتوژنز بیماری آلزایمر نشان می‌دهد که عدم تعادل بین تولید و پاکسازی آمیلوئید)  β- (Aβعامل توسعه زوال عقل است. فعالیت ورزشی رسوب Aβ را از طریق مسیر سیگنال‌دهی AMPK کاهش می‌دهد. علاوه بر این، رزوراترول (RSV) دارای اثرات محافظت‌کننده عصبی مرتبط با زوال شناختی است. هدف از پژوهش حاضر بررسی اثر تمرین هوازی و مصرف رزوراترول بر مسیر AMPK/PGC-1α/SIRT1 هیپوکامپ موش‌های مبتلا با آلزایمر بود.
مواد و روش ها: در این مطالعه تجربی، 35 سر موش صحرایی نر نژاد ویستار در پنج گروه کنترل (NO)، آلزایمر (AD)، آلزایمر-تمرین (ADT)، آلزایمر-رزوراترول (ADRSV) و آلزایمر-تمرین-رزوراترول (ADTRSV) قرار گرفتند. گروه های مکمل، طی دوره مداخله روزانه 20 میلی‌گرم RSV (به ازای هر کیلوگرم وزن بدن) را به صورت خوراکی دریافت کردند. برنامه تمرین هوازی شامل دویدن روی تردمیل با سرعت 18-6 متر در دقیقه، پنج روز هفته به مدت هشت هفته اجرا شد.
نتایج: القای AD باعث کاهش معنی‌داری در بیان ژن AMPK/PGC-1α/SIRT1 شد (0001/0=p). تمرین و RSV باعث افزایش معنی‌داری بیان ژن AMPK/PGC-1α/SIRT1 در موش‌های صحرایی AD شد (p<0.05). همچنین افزایش معنی‌داری در میزان تغییرات بیان ژن AMPK، PGC-1α و SIRT1 در گروه ADTRSV نسبت به گروه‌ ADT ( به ترتیب 034/0p=، 020/0p= و 038/0p=) و ADRSV (026/0p=، 021/0p= و 021/0p=) مشاهده شد.
نتیجه‌گیری: القای AD با کاهش بیان ژن AMPK/PGC-1α/SIRT1 همراه بود و فعالیت ورزشی هوازی و مصرف RSV قادر است این روند را معکوس کند. به نظر تغییر سطوح این شاخص‌ها به دنبال فعالیت‌بدنی و استفاده از RSV می‌تواند تا حدی عوارض بیماری AD را کاهش دهد.

کلیدواژه‌ها

عنوان مقاله [English]

The synergistic role of aerobic training and resveratrol consumption on the pathway of hippocampal mitochondrial biogenesis in rats with Alzheimer's disease

نویسندگان [English]

  • Ammar Rashet
  • Ahmad Abdi
  • Alireza Barari
Department of Physical Education and Sport Science, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
چکیده [English]

Background and Objective: The pathogenesis of AD shows that the imbalance between the production and clearance of amyloid-β (Aβ) is the cause of the development of dementia. Exercise reduces Aβ deposition through the AMPK signaling pathway. In addition, resveratrol (RSV) has neuroprotective effects associated with cognitive decline. The aim of the present study was to investigate the effect of aerobic training and RSV consumption on the AMPK/PGC-1α/SIRT1 pathway in the hippocampus of rats with Alzheimer's disease.
Materials and Methods: In this experimental study, 35 male Wistar rats were divided into 5 groups: Control (NO), Alzheimer's (AD), Alzheimer's-Training (ADT), Alzheimer's-Resveratrol (ADRSV) and Alzheimer's-Training-Resveratrol (ADTRSV). The supplement groups received 20 mg of RSV (per kg of body weight) orally during the intervention period. Aerobic exercise program including running on treadmill with a speed of 6-18 meters per minute, was performed 5 days a week for eight weeks.
Results: AD induction caused a significant decrease in the gene expression of AMPK/PGC-1α/SIRT1 (p=0.0001). Exercise and RSV significantly increased the gene expression of AMPK/PGC-1α/SIRT1 in AD rats (p<0.05). Also, a significant increase was observed in the gene expression changes of AMPK, PGC-1α and SIRT1 in the ADTRSV group compared to the ADT group (p=0.034, p=0.020 and p=0.038, respectively) and ADRSV (p=0.026, p=0.021 and p=0.021).
Conclusion: AD induction was associated with a decrease in AMPK/PGC-1α/SIRT1 gene expression, and aerobic exercise and RSV consumption can reverse this process. It seems that changing the levels of these indicators following physical activity and the use of RSV can partially reduce the complications of AD.

کلیدواژه‌ها [English]

  • Exercise
  • Resveratrol
  • Mitochondrial biogenesis
  • Alzheimer's disease

مراجع

  1. Ngolab J, Honma P, Rissman RA. Reflections on the utility of the retina as a biomarker for Alzheimer’s disease: a literature review. Neurology and Therapy 2019;8:57-72.
  2. Ju Y, Tam KY. Pathological mechanisms and therapeutic strategies for Alzheimer’s disease. Neural Regeneration Research 2022;17(3):543.
  3. Cioffi F, Adam RHI, Broersen K. Molecular mechanisms and genetics of oxidative stress in Alzheimer’s disease. Journal of Alzheimer's Disease 2019;72(4):981-1017.
  4. Kjøbsted R, Hingst JR, Fentz J, Foretz M, Sanz M-N, Pehmøller C, et al. AMPK in skeletal muscle function and metabolism. The FASEB Journal 2018;32(4):1741.
  5. Koo J-H, Kang E-B, Oh Y-S, Yang D-S, Cho J-Y. Treadmill exercise decreases amyloid-β burden possibly via activation of SIRT-1 signaling in a mouse model of Alzheimer's disease. Experimental Neurology 2017;288:142-52.
  6. Engels M, Van der Flier W, Stam C, Hillebrand A, Scheltens P, Van Straaten E. Alzheimer’s disease: the state of the art in resting-state magnetoencephalography. Clinical Neurophysiology 2017;128(8):1426-37.
  7. Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, Aisen PS, et al. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. Journal of Neuroinflammation 2017;14:1-10.
  8. Witte AV, Kerti L, Margulies DS, Flöel A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. Journal of Neuroscience 2014;34(23):7862-70.
  9. Broderick TL, Rasool S, Li R, Zhang Y, Anderson M, Al-Nakkash L, et al. Neuroprotective effects of chronic resveratrol treatment and exercise training in the 3xTg-AD mouse model of Alzheimer’s disease. International Journal of Molecular Sciences 2020;21(19):7337.
  10. Allard J, Graham-Hyatt S, Mulgrave V, Alsayegh A. Exercise-induced upregulation of APOE expression is attenuated by dietary supplementation with resveratrol. Physiology 2023;38(S1):5735198.
  11. 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. Journal of Ilam University of Medical Sciences 2019; 27 (1) :1-12.
  12. 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.
  13. Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2009;458(7241):1056-60.
  14. Dong W, Wang F, Guo W, Zheng X, Chen Y, Zhang W, et al. Aβ25–35 suppresses mitochondrial biogenesis in primary hippocampal neurons. Cellular and Molecular Neurobiology 2016;36:83-91.
  15. 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.
  16. Jia J, Yin J, Zhang Y, Xu G, Wang M, Jiang H, et al. Thioredoxin-1 Promotes Mitochondrial Biogenesis Through Regulating AMPK/Sirt1/PGC1α Pathway in Alzheimer's Disease. ASN neuro. 2023;15:17590914231159226.
  17. Walia V, Kaushik D, Mittal V, Kumar K, Verma R, Parashar J, et al. Delineation of neuroprotective effects and possible benefits of antioxidantstherapy for the treatment of Alzheimer’s diseases by targeting mitochondrial-derived reactive oxygen species: bench to bedside. Molecular Neurobiology 2021;59(1):657-680.
  18. Silva P, Vauzour D. Wine polyphenols and neurodegenerative diseases: An update on the molecular mechanisms underpinning their protective effects. Beverages. 2018;4(4):96.
  19. Azarian F, Farsi S, Hosseini SA, Azarbayjani MA. Effect of endurance training with saffron consumption on PGC1-α gene expression in hippocampus tissue of rats with Alzheimer’s disease. Annals of Military and Health Sciences Research 2020;18(1).
  20. Lin J-Y, Kuo W-W, Baskaran R, Kuo C-H, Chen Y-A, Chen WS-T, et al. Swimming exercise stimulates IGF1/PI3K/Akt and AMPK/SIRT1/PGC1α survival signaling to suppress apoptosis and inflammation in aging hippocampus. Aging 2020;12(8):6852.
  21. Sung B, Chung JW, Bae HR, Choi JS, Kim CM, Kim ND. Humulus japonicus extract exhibits antioxidative and anti‑aging effects via modulation of the AMPK‑SIRT1 pathway. Experimental and Therapeutic Medicine 2015;9(5):1819-26.
  22. Gerhart-Hines Z, Rodgers J, Bare O, Lerin C, Kim S, Mostoslavsky R. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1a. EMBO Journal 1923;26:1913.
  23. Ghasemi E, Afzalpour ME, Zarban A. The effects of 10 weeks of high-intensity interval training and green tea supplementation on serum levels of sirtuin 1 and catalase in overweight women. Sport Physiology 2016;8(32):169-84.
  24. Cosín-Tomàs M, Senserrich J, Arumí-Planas M, Alquézar C, Pallàs M, Martín-Requero Á, et al. Role of resveratrol and selenium on oxidative stress and expression of antioxidant and anti-aging genes in immortalized lymphocytes from Alzheimer’s disease patients. Nutrients. 2019;11(8):1764.
  25. Scarpulla RC. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 2011;1813(7):1269-78.
  26. Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, North BJ, et al. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metabolism 2012;15(5):675-90.
  27. Maugeri A, Barchitta M, Mazzone MG, Giuliano F, Basile G, Agodi A. Resveratrol modulates SIRT1 and DNMT functions and restores LINE-1 methylation levels in ARPE-19 cells under oxidative stress and inflammation. International Journal of Molecular Sciences 2018;19(7):2118.
  28. Ma X, Sun Z, Han X, Li S, Jiang X, Chen S, et al. Neuroprotective effect of resveratrol via activation of Sirt1 signaling in a rat model of combined diabetes and Alzheimer’s disease. Frontiers in Neuroscience 2020;13:1400.
  29. 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.
  30. Lin C-H, Lin C-C, Ting W-J, Pai P-Y, Kuo C-H, Ho T-J, et al. Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts. Age 2014;36:1-10.
دانشور پزشکی
دوره 32، شماره 2 - شماره پیاپی 171
خرداد و تیر 1403
صفحه 52-62

فایل ها

هم رسانی

ارجاع به این مقاله

آمار