نوع مقاله : مقاله پژوهشی
نویسندگان
1 دانشجوی دکتری فیزیولوژی ورزشی، گروه تربیت بدنی و علوم ورزشی، دانشکده علوم انسانی، دانشگاه تربیت مدرس تهران، ایران.
2 استاد فیزیولوژی ورزشی، گروه تربیت بدنی و علوم ورزشی، دانشکده علوم انسانی، دانشگاه تربیت مدرس تهران، ایران
3 استاد فیزیولوژی، گروه فیزولوژی و فارماکولوژی، موسسه پاستور، تهران ، ایران
4 دانشجوی دکتری فیزیولوژی ورزشی، گروه تربیت بدنی و علوم ورزشی، دانشکده علوم انسانی، دانشگاه تربیت مدرس تهران، ایران
5 دانشجوی دکتری فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه خوارزمی تهران، ایران
چکیده
زمینه و هدف: مطالعات پیشین نشان داده اند که عامل نوروتروفیک مشتق شده از مغز (BDNF) در القاء اثرات مفید فعالیت ورزشی بر مغز به ویژه هیپوکامپ نقش بسیار حیاتی دارد. با این وجود مسیرهای پیام دهی درگیر در افزایش BDNF ناشی از تمرین ورزشی اجباری در هیپوکامپ به خوبی شناخته نشده است. از این رو، هدف از مطالعه حاضر بررسی تأثیر هشت هفته تمرین اجباری نوارگردان با شدت کم بر بیان ژن های گیرنده فعال کننده تکثیر پروکسی زوم گاما هم فعال ساز آلفا (PGC-1α)، فیبرونکتین نوع 3 حاوی پروتئین 5 (FNDC5) و BDNFدر هیپوکامپ موش های صحرایی نر بود. روش تحقیق: تعداد 18 سر موش صحرائی نر نژاد ویستار به طور تصادفی به 3 گروه کنترل (6 سر)، شم (6 سر) و تمرین اجباری (6 سر) تقسیم شدند. حیوانات در گروه تمرین ورزشی به انجام 8 هفته تمرین اجباری (5 جلسه در هفته) با شدت پایین (سرعت 15 متر بر دقیقه) بر روی نوارگردان پرداختند. 24 ساعت پس از آخرین جلسة تمرینی همه موش ها بی هوش شدند. سر حیوانات جدا شد و هیپوکامپ استخراج گردید و در دمای 80- درجة سانتیگراد برای تجزیه تحلیل های بعدی نگهداری شد. به منظور سنجش میزان بیان ژن ها در هیپوکامپ از روش واکنش زنجیره پلیمراز زمان واقعی (Real-Time-PCR) استفاده شد. داده ها با روش تحلیل واریانس یکطرفه و آزمون تعقیبی توکی در سطح 05/0>p تجزیه تحلیل شد. یافته ها: نتایج این تحقیق نشان داد سطوح ژن های PGC-1α (003/0P<)، FNDC5 (006/0P<) و BDNF (02/0P<) در گروه تمرین اجباری نسبت به گروه کنترل به طور معنی داری بالاتر بود. اما تفاوتی بین گروه شم و کنترل در میزان mRNA ژنها مشاهده نشد. نتیجه گیری: به نظر میرسد تمرین اجباری با شدت کم احتمالاً از مسیر پیام دهی وابسته به PGC-1αمنجر به افزایش بیان FNDC5 و در نتیجه افزایش بیان BDNF میگردد. بنابراین، این نوع از تمرین ورزشی را می توان به منظور القاء اثرات مفید ورزش بر هیپوکامپ، به کار گرفت.
کلیدواژه‌ها
عنوان مقاله [English]
The effect of the treadmill running on genes expression ofthePGC-1α, FNDC5 and BDNF in hippocampus of male rats
نویسندگان [English]
- Seyyed Mohammad Ali Azimi Dokht 1
- Reaz Gharakhanlou 2
- Naser Naghdi 3
- Davar Khodadadi 4
- Ali Asghar Zare Zade Mehrizi 5
1 PhD Student of Exercise Physiology, Department of Physical Education and Sport Sciences, Faculty of Humanities, TarbiatModares University, Tehran, Iran.
2 Professor, Department of Physical Education and Sport Sciences, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran
3 Professor, Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran
4 PhD Student of Exercise Physiology, Department of Physical Education and Sport Sciences, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran
5 PhD Student of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Kharazmi University, Tehran, Iran
چکیده [English]
Background and Aim: Previous studies have shown that brain-derived neurotrophic factor (BDNF) plays a vital role to induce the beneficial effects of exercise on the brain, especially the hippocampus. However, signaling pathways related to increasing BDNF induced by forced exercise in hippocampus not well known. Therefore, the purpose of current study was to investigate the effect of 8-weeks of low-intensity forced treadmill training on genes expression of peroxisome proliferator activated receptor-gamma co-activator 1-alpha (PGC-1α), Fibronectin type III domain containing 5 (FNDC5) and BDNF in hippocampus of male rats. Materials and Methods: Eighteen male Wistar rats were randomly divided into 3 groups: Control (n=6), Sham (n=6) and Forced training (n=6). Animals in the training group performed 8 weeks of forced training (5 sessions per week) with low-intensity (speed: 15 m/min) on the treadmill. Twenty-four hours after last session of exercise, rats were decapitated and the hippocampus were carefully removed and rapidly frozen in liquid nitrogen, and finally stored at -80°C for further analysis. Real-Time-PCR method was used to measure the expression of genes in the hippocampus. Data were analyzed by one way ANOVA and Tukey post hoc test at the significant level of p<0.05.Results: The results of showed that mRNA levels of PGC-1α(p<0.003), FNDC5 (p<0.006) and BDNF(p<0.02) in the forced training group were significantly higher than the control group. However, there was no significant difference in the mRNA levels of genes between the sham and control groups. Conclusion: It seems that the low-intensity forced training, likely through a PGC-1α-dependent signaling pathway, leads to increasing expression of FNDC5 and as a result causes increasing the expression of BDNF. Thus, this type exercise training can be used as induction of beneficial effects of exercise on the hippocampus.
کلیدواژه‌ها [English]
- low-intensityforced Training
- PGC-1α
- FNDC5
- BDNF
- Rat Hippocampus
Ang, E., & Gomez-Pinilla, F. (2007). Potential therapeutic effects of exercise to the brain. Current Medicinal Chemistry, 14(24), 2564-2571.
Arida, R. M., Scorza, C. A., da Silva, A. V., Scorza, F. A., & Cavalheiro, E. A. (2004). Differential effects of spontaneous versus forced exercise inrats on the staining of parvalbumin-positive neurons in the hippocampal formation. Neuroscience Letters, 364(3), 135-138.
Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., ... & Kajimura, S. (2012). A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, 481(7382), 463.
Buchman, A., Boyle, P., Yu, L., Shah, R., Wilson, R., & Bennett, D. (2012). Total daily physical activity and the risk of AD and cognitive decline in older adults. Neurology, 78(17), 1323-1329.
Chen, M. J., & Russo-Neustadt, A. A. (2005). Exercise activates the phosphatidylinositol 3-kinase pathway. Molecular Brain Research, 135(1), 181-193.
Cotman, C. W., Berchtold, N. C., & Christie, L. A. (2007). Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends in Neurosciences, 30(9), 464-472.
Dao, A. T., Zagaar, M. A., & Alkadhi, K. A. (2015). Moderate treadmill exercise protects synaptic plasticity of the dentate gyrus and related signaling cascade in a rat model of Alzheimer’s disease. Molecular Neurobiology, 52(3), 1067-1076.
Farmer, J., Zhao, X., Van Praag, H., Wodtke, K., Gage, F., & Christie, B. (2004). Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague–Dawley rats in vivo. Neuroscience, 124(1), 71-79.
Farshbaf, M. J., Ghaedi, K., Megraw, T. L., Curtiss, J., Faradonbeh, M. S., Vaziri, P., & Nasr-Esfahani, M. H. (2016). Does PGC1α/FNDC5/BDNF elicit the beneficial effects of exercise on neurodegenerative disorders?. Neuromolecular Medicine, 18(1), 1-15.
Finck, B. N., & Kelly, D. P. (2006). PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. The Journalof Clinical Investigation, 116(3), 615-622.
Hashemi, M. S., Ghaedi, K., Salamian, A., Karbalaie, K., Emadi-Baygi, M., Tanhaei, S., ... & Baharvand, H. (2013). Fndc5 knockdown significantly decreased neural differentiation rate of mouse embryonic stem cells. Neuroscience, 231, 296-304.
Kim, S. E., Ko, I. G., Shin, M. S., Kim, C. J., Jin, B. K., Hong, H. P., & Jee, Y. S. (2013). Treadmill exercise and wheel exercise enhance expressions of neutrophic factors in the hippocampus of lipopolysaccharide-injected rats. Neuroscience Letters, 538, 54-59.
Leasure, J. L., & Jones, M. (2008). Forced and voluntary exercise differentially affect brain and behavior. Neuroscience, 156(3), 456-465.
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods, 25(4), 402-408.
Mattson, M. P. (2012). Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell Metabolism, 16(6), 706-722.
Molteni, R., Wu, A., Vaynman, S., Ying, Z., Barnard, R. J., & Gomez-Pinilla, F. (2004). Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor. Neuroscience, 123(2), 429-440.
Murray, P. S., & Holmes, P. V. (2011). An overview of brain-derived neurotrophic factor and implications for excitotoxic vulnerability in the hippocampus. International Journal of Peptides, 146(7), 347-356.
Ploughman, M., Granter-Button, S., Chernenko, G., Tucker, B. A., Mearow, K. M., & Corbett, D. (2005). Endurance exercise regimens induce differential effects on brain-derived neurotrophic factor, synapsin-I and insulin-like growth factor I after focal ischemia. Neuroscience, 136(4), 991-1001.
Rosa E., Fahnestock M. (2014) Amyloid-Beta, BDNF, and the mechanism of neurodegeneration in alzheimer’s disease. In: Kostrzewa R. (eds) Handbook of Neurotoxicity. Springer, New York, NY.
Sheikhzadeh, F., Etemad, A., Khoshghadam, S., Asl, N. A., & Zare, P. (2015). Hippocampal BDNF content in response to short-and long-term exercise. Neurological Sciences, 36(7), 1163-1166.
Soya, H., Nakamura, T., Deocaris, C. C., Kimpara, A., Iimura, M., Fujikawa, T., ... & Nishijima, T. (2007). BDNF induction with mild exercise in the rat hippocampus. Biochemical and Biophysical Research Communications, 358(4), 961-967.
Spiegelman, B. M. (2007). Transcriptional control of mitochondrial energy metabolism through the PGC1 coactivators. In Novartis Foundation Symposium 287, 60. Chichester; New York; John Wiley; 1999.
Steiner, J. L., Murphy, E. A., McClellan, J. L., Carmichael, M. D., & Davis, J. M. (2011). Exercise training increases mitochondrial biogenesis in the brain. Journal of Applied Physiology, 111(4), 1066-1071.
Vaynman, S., Ying, Z., & Gomez‐Pinilla, F. (2004). Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. European Journal of Neuroscience, 20(10), 2580-2590.
Wrann, C. D. (2015). FNDC5/Irisin–their role in the nervous system and as a mediator for beneficial effects of exercise on the brain. Brain Plasticity, 1(1), 55-61.
Wrann, C. D., White, J. P., Salogiannnis, J., Laznik-Bogoslavski, D., Wu, J., Ma, D., ... & Spiegelman, B. M. (2013). Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metabolism, 18(5), 649-659.
Yanagita, S., Amemiya, S., Suzuki, S., & Kita, I. (2007). Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats. Life Sciences, 80(4), 356-363.
Yu, L., & Yang, S. J. (2010). AMP-activated protein kinase mediates activity-dependent regulation of peroxisome proliferator-activated receptor γ coactivator-1α and nuclear respiratory factor 1 expression in rat visual cortical neurons. Neuroscience, 169(1), 23-38.
Zagaar, M., Dao, A., Levine, A., Alhaider, I., & Alkadhi, K. (2013). Regular exercise prevents sleep deprivation associated impairment of long-term memory and synaptic plasticity in the CA1 area of the hippocampus. Sleep, 36(5), 751-761.
)