نوع مقاله : مقاله پژوهشی Released under (CC BY-NC) license I Open Access I
نویسندگان
1 دانشجو ی دکتری فیزیولوژی ورزشی، پردیس ارس دانشگاه تهران، تبریز، ایران
2 استاد، گروه فیزیولوژی فعالیت ورزشی، دانشکده علوم ورزشی و تندرستی دانشگاه تهران، دانشگاه تهران، ایران
3 استادیار، گروه فیزیولوژی فعالیت ورزشی، دانشکده علوم ورزشی و تندرستی دانشگاه تهران، دانشگاه تهران، ایران
4 دانشیار، گروه فیزیولوژی فعالیت ورزشی، دانشکده علوم ورزشی و تندرستی دانشگاه تهران، دانشگاه تهران، ایران
چکیده
هدف: استرس اکسیداتیو یکی از عوامل مهم در تشدید وضعیت صرع و تحریک پذیری نورون ها و افزایش حملات می باشد. در این پژوهش قصد داریم به بررسی تاثیر هشت هفته تمرین هوازی بر بیان miR-23a، سطوح MDA و فعالیت آنزیم آنتی اکسیدانی CAT در هیپوکمپ و تعداد حملات در رت های مبتلا به صرع بپردازیم.
روش‌شناسی: در این مطالعه، ۳۲ سر رت نر نژاد ویستار (۴–۶ هفته‌ای) به چهار گروه شامل گروه سالم، گروه شم، گروه صرع، و گروه صرع + تمرین هوازی تقسیم شدند. برای القای صرع، تزریق درون‌هیپوکمپی کاینیک اسید به کار رفت و شدت حملات بر اساس مقیاس راسین ارزیابی گردید. پروتکل تمرینی شامل ۸ هفته تمرین هوازی با شدت متوسط، پنج جلسه در هفته و هر جلسه به مدت ۴۰ دقیقه بود. چهل و هشت ساعت پس از آخرین جلسه تمرینی، حیوانات با کتامین و زایلازین بیهوش و بافت هیپوکمپ آن‌ها استخراج شد. به منظور سنجش فعالیت آنزیم CAT و سطوح MDA از روش الایزا استفاده گردید. همچنین برای بررسی بیان miR-23a روش Real-time PCR به کار گرفته شد.
یافته‌ها: فعالیت ورزشی هوازی سطوح MDA ( 007/0 =P ) و بیان miR-23a ( 53/0 =P ) را در هیپوکمپ رت های مبتلا به صرع کاهش داد و فعالیت آنزیم CAT را ( 02/0 =P ) افزایش داد. تعداد حملات نیز به طور معنی داری در رت های مبتلا به صرع کاهش یافت( 01/0 =P ).
نتیجه‌گیری: هشت هفته فعالیت ورزشی منظم میتواند منجر به کاهش در پرواکسیداسیون چربی ها و همینطور افزایش در آنزیم آنتی اکسیدانی CAT در هیپوکمپ شود و این بهبود در وضعیت آنتی اکسیدانی با کاهش تعداد تشنج همراه بود.
کلیدواژه‌ها
موضوعات
عنوان مقاله [English]
The Effect of Eight Weeks of Moderate-Intensity Aerobic Exercise on the Expression of MicroRNA-23a, MDA Levels, and CAT Enzyme Activity in the Hippocampus of Epileptic Rats
نویسندگان [English]
- Sabah Rezagholi 1
- Mohammad Reza Kordi 2
- Amir Hossein Saffar Kohneh Quchan 3
- Reza Nouri 4
1 PhD Student in Exercise Physiology, Aras International Campus, University of Tehran, Tabriz, Iran
2 Professor, Department of Exercise Physiology, Faculty of Sport Sciences and Health, University of Tehran, Tehran, Iran
3 Assistant Professor, Department of Exercise Physiology, Faculty of Sport Sciences and Health, University of Tehran, Tehran, Iran
4 Associate Professor, Department of Exercise Physiology, Faculty of Sport Sciences and Health, University of Tehran, Tehran, Iran
چکیده [English]
Objective: Oxidative stress is a important factor in exacerbating epilepsy, neuronal hyperexcitability, and increased seizure frequency. This study aimed to investigate the effects of aerobic exercise on hippocampal miR-23a expression, malondialdehyde (MDA) levels and catalase (CAT) enzyme activity, and seizure frequency in rats with epilepsy.
Methodology: In this study, thirty-two male Wistar rats (4–6 weeks old) were randomly assigned to four groups: healthy, sham, epileptic, and epileptic + aerobic training. Epilepsy was induced by intra-hippocampal injection of kainic acid, and seizure severity was evaluated using the Racine scale. The training protocol consisted of moderate-intensity aerobic exercise performed for eight weeks, five sessions per week, with each session lasting 40 minutes. Forty-eight hours after the last training session, the animals were anesthetized with ketamine and xylazine, and the hippocampal tissue was extracted. Catalase (CAT) activity and malondialdehyde (MDA) levels were measured using the ELISA method, while the expression of miR-23a was assessed by real-time PCR.
Results: Aerobic exercise reduced hippocampal MDA levels (P=0.007) and miR-23a expression (P=0.53) while increasing CAT enzyme activity (P=0.02) in epileptic rats. Seizure frequency was also significantly decreased in the epileptic rats (P=0.01).
Conclusion: Eight weeks of regular exercise can lead to a reduction in lipid peroxidation and an increase in the antioxidant enzyme CAT in the hippocampus. This improvement in antioxidant status was associated with a decrease in the number of seizures.
کلیدواژه‌ها [English]
- Oxidative stress
- Seizure
- Regular exercise
- Lipid peroxidation
Aguiar CCT, Almeida AB, Araújo PVP, Abreu RNDCd, Chaves EMC, Vale OCd, et al. Oxidative stress and epilepsy: literature review. Oxidative medicine and cellular longevity. 2012;2012(1):795259.
- Pearson-Smith JN, Patel M. Metabolic dysfunction and oxidative stress in epilepsy. International Journal of Molecular Sciences. 2017;18(11):2365.
- Lee KH, Cha M, Lee BH. Neuroprotective effect of antioxidants in the brain. International journal of molecular sciences. 2020;21(19):7152.
- Liang L, Ho Y, Patel M. Mitochondrial superoxide production in kainate-induced hippocampal damage. Neuroscience. 2000;101(3):563-70.
- Martinc B, Grabnar I, Vovk T. The role of reactive species in epileptogenesis and influence of antiepileptic drug therapy on oxidative stress. Current Neuropharmacology. 2012;10(4):328-43.
- Albano E, Bellomo G, Parola M, Carini R, Dianzani MU. Stimulation of lipid peroxidation increases the intracellular calcium content of isolated hepatocytes. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 1991;1091(3):310-6.
- Morrow JD. The isoprostanes: their quantification as an index of oxidant stress status in vivo. Drug metabolism reviews. 2000;32(3-4):377-85.
- Waldbaum S, Patel M. Mitochondrial dysfunction and oxidative stress: a contributing link to acquired epilepsy? Journal of bioenergetics and biomembranes. 2010;42:449-55.
- Freitas RM, Vasconcelos SM, Souza FC, Viana GS, Fonteles MM. Oxidative stress in the hippocampus after pilocarpine‐induced status epilepticus in Wistar rats. The FEBS journal. 2005;272(6):1307-12.
- Barros DO, Xavier SM, Barbosa CO, Silva RF, Freitas RL, Maia FD, et al. Effects of the vitamin E in catalase activities in hippocampus after status epilepticus induced by pilocarpine in Wistar rats. Neurosci Lett. 2007;416(3):227-30.
- Menon B, Ramalingam K, Kumar RV. Low plasma antioxidant status in patients with epilepsy and the role of antiepileptic drugs on oxidative stress. Annals of Indian Academy of Neurology. 2014;17(4):398-404.
- Wang J, Zhao J. MicroRNA Dysregulation in Epilepsy: From Pathogenetic Involvement to Diagnostic Biomarker and Therapeutic Agent Development. Front Mol Neurosci. 2021;14:650372.
- Henshall DC, Hamer HM, Pasterkamp RJ, Goldstein DB, Kjems J, Prehn JH, et al. MicroRNAs in epilepsy: pathophysiology and clinical utility. The Lancet Neurology. 2016;15(13):1368-76.
- Zhu X, Zhang A, Dong J, Yao Y, Zhu M, Xu K, Al Hamda MH. MicroRNA-23a contributes to hippocampal neuronal injuries and spatial memory impairment in an experimental model of temporal lobe epilepsy. Brain Research Bulletin. 2019;152:175-83.
- Ribarič S. Physical exercise, a potential non-pharmacological intervention for attenuating neuroinflammation and cognitive decline in Alzheimer’s disease patients. International journal of molecular sciences. 2022;23(6):3245.
- Häfele CA, Freitas MP, da Silva MC, Rombaldi AJ. Are physical activity levels associated with better health outcomes in people with epilepsy? Epilepsy & Behavior. 2017;72:28-34.
- Allendorfer JB, Brokamp GA, Nenert R, Szaflarski JP, Morgan CJ, Tuggle SC, et al. A pilot study of combined endurance and resistance exercise rehabilitation for verbal memory and functional connectivity improvement in epilepsy. Epilepsy & Behavior. 2019;96:44-56.
- Feter N, Alt R, Häfele CA, da Silva MC, Rombaldi AJ. Effect of combined physical training on cognitive function in people with epilepsy: results from a randomized controlled trial. Epilepsia. 2020;61(8):1649-58.
- McAuley JW, Long L, Heise J, Kirby T, Buckworth J, Pitt C, et al. A prospective evaluation of the effects of a 12-week outpatient exercise program on clinical and behavioral outcomes in patients with epilepsy. Epilepsy & Behavior. 2001;2(6):592-600.
- Hrncic D, Rasic-Markovic A, Lekovic J, Krstic D, Colovic M, Macut D, et al. Exercise decreases susceptibility to homocysteine seizures: the role of oxidative stress. International journal of sports medicine. 2014;35(07):544-50.
- Kim H-j, Kim I-K, Song W, Lee J, Park S. The synergic effect of regular exercise and resveratrol on kainate-induced oxidative stress and seizure activity in mice. Neurochemical research. 2013;38:117-22.
- Kim H-j, Song W, Jin EH, Kim J, Chun Y, An EN, Park S. Combined low-intensity exercise and ascorbic acid attenuates kainic acid-induced seizure and oxidative stress in mice. Neurochemical research. 2016;41:1035-41.
- Racine RJ. Modification of seizure activity by electrical stimulation: II. Motor seizure. Electroencephalography and clinical neurophysiology. 1972;32(3):281-94.
- Arida RM, Sanabria ERG, da Silva AC, Faria LC, Scorza FA, Cavalheiro EA. Physical training reverts hippocampal electrophysiological changes in rats submitted to the pilocarpine model of epilepsy. Physiology & behavior. 2004;83(1):165-71.
- Patel MN. Oxidative stress, mitochondrial dysfunction, and epilepsy. Free radical research. 2002;36(11):1139-46.
- Geronzi U, Lotti F, Grosso S. Oxidative stress in epilepsy. Expert review of neurotherapeutics. 2018;18(5):427-34.
- Puttachary S, Sharma S, Stark S, Thippeswamy T. Seizure‐induced oxidative stress in temporal lobe epilepsy. BioMed research international. 2015;2015(1):745613.
- Méndez-Armenta M, Nava-Ruíz C, Juárez-Rebollar D, Rodríguez-Martínez E, Yescas Gómez P. Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy. Oxidative medicine and cellular longevity. 2014;2014(1):293689.
- Sudha K, Rao AV, Rao A. Oxidative stress and antioxidants in epilepsy. Clinica Chimica Acta. 2001;303(1-2):19-24.
- Çevik M, Varol S, Yücel Y, Akıl E, Çelepkolu T, Arıkanoğlu A, et al. Serum paraoxonase-1 activities and malondialdehyde levels in patients with epilepsy. Dicle Med J. 2012;39(4):557-60.
- Shehta N, Kamel AE, Sobhy E, Ismail MH. Malondialdehyde and superoxide dismutase levels in patients with epilepsy: a case–control study. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery. 2022;58(1):51.
- Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH, Bach JH, et al. Role of oxidative stress in epileptic seizures. Neurochem Int. 2011;59(2):122-37.
- Parsons ALM, Bucknor EMV, Castroflorio E, Soares TR, Oliver PL, Rial D. The Interconnected Mechanisms of Oxidative Stress and Neuroinflammation in Epilepsy. Antioxidants. 2022;11(1):157.
- Cavalcante BRR, Improta-Caria AC, Melo VH, De Sousa RAL. Exercise-linked consequences on epilepsy. Epilepsy Behav. 2021;121(Pt A):108079.
- Done AJ, Traustadóttir T. Nrf2 mediates redox adaptations to exercise. Redox Biol. 2016;10:191-9.
- Cetinkaya A, Demir S, Orallar H, Kayacan Y, Beyazcicek E. The effects of treadmill exercise on oxidative stress in Mongolian gerbils with penicillin-induced epilepsy. Experimental Biomedical Research. 2018;1(1):10.
- Soleimani Meigoni Z, Jabari F, Motaghinejad M, Motevalian M. Protective effects of forced exercise against topiramate-induced cognition impairment and enhancement of its antiepileptic activity: molecular and behavioral evidences. International Journal of Neuroscience. 2022;132(12):1198-209.
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