اثر تمرین استقامتی بعد از القای آلزایمر بر برخی عوامل مرتبط با نوروپلاستیسیته در هیپوکمپ موش های نر نژاد ویستار

محورهای موضوعی : فصلنامه زیست شناسی جانوری

سجاد رجبی امیری ¹ (گروه فیزیولوژی ورزشی، گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران)
علیرضا براری ² (گروه فیزیولوژی ورزشی، گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران)
احمد عبدی ³ (گروه فیزیولوژی ورزشی، گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران)

تاریخ دریافت : 1400/03/25 تاریخ پذیرش : 1400/06/21 تاریخ انتشار : 1400/12/01

کلید واژه: آلزایمر, BDNF, هیپوکمپ, PKG, cGMP,

چکیده مقاله :

میلیون ها نفر در سراسر جهان به بیماری آلزایمر مبتلا هستند و با رشد نامتناسب جمعیت مسن، این بیماری که رایج ترین شکل زوال عقل در میان افراد مسن است، در حال تبدیل شدن به یک بحران سلامتی عمومی است. هدف از پژوهش حاضر بررسی اثر تمرین استقامتی قبل و بعد از القای آلزایمر بر برخی عوامل مرتبط با نوروپلاستیسیته در هیپوکمپ موش های نر نژاد ویستار بود. 32 سر رت نر بالغ 8 هفته ای با میانگین وزنی 17 ± 250 گرم، قبل از القای آلزایمر به صورت تصادفی به 2 گروه استراحت (16 سر) و تمرین (16 سر) تقسیم شدند. پس از 4 هفته (هفته اول و دوم با سرعت 10 متر بر دقیقه در دو نوبت 15 دقیقه‌ای، هفته سوم با سرعت 15 متر بر دقیقه در سه نوبت 15 دقیقه‌ای و در هفته چهارم با سرعت 15 متر بر دقیقه در چهار نوبت 15 دقیقه‌ای با وقفه 5 دقیقه‌ای)، هر گروه به دو زیرگروه: 1. تزریق آمیلوئیدبتا و 2. بدون تزریق تقسیم شدند. پس از 72 ساعت حیوانات کشته و هیپوکمپ آن ها جهت بررسی برداشته شد. بیان ژن BDNF، PKG و cGMP با روش Real Time PCR اندازه گیری شد. داده ها به روش تحلیل واریانس یک طرفه و آزمون تعقیبی توکی در سطح معنی داری 05/0 p < تجزیه و تحلیل شدند. نتایج نشان داد که سطح BDNF، PKG و cGMP در گروه تمرین نسبت به گروه استراحت در مرحله بعد از القای آلزایمر به طوری معنی داری بیشتر بود (001/0= p). با توجه به نتایج، به نظر می رسد تمرین هوازی می تواند به بهبود نوروپلاستیسیته در هیپوکمپ موش های آلزایمری کمک کند.

چکیده انگلیسی:

Millions of people worldwide have Alzheimer's disease, and with the disproportionate growth of the elderly population, the disease, which is the most common form of dementia among the elderly, is becoming a public health crisis. This study aimed to investigate the effect of endurance training before and after Alzheimer's induction on some neuroplasticity-related factors in the hippocampus of male Wistar rats. Before inducing Alzheimer's disease, 32 8-week-old male rats weighing an average of 250 g were randomly allocated into two groups: rest (16 heads) and exercise (16 heads). Each group was divided into two subgroups after four weeks (the first and second weeks at a speed of 10 meters per minute in two 15-minute shifts, the third week at a speed of 15 meters per minute in three 15-minute shifts, and the fourth week at a speed of 15 meters per minute in four 15-minute shifts with 5-minute intervals).1. amyloid beta injection and 2. without injection. After 72 hours, the animals were killed and their hippocampus was removed for examination. Real Time PCR measured BDNF, PKG, and cGMP gene expression.Data were analyzed by one-way analysis of variance and Tukey post hoc test at the significant level of p <0.05. The results showed that the levels of BDNF, PKG and cGMP in the exercise group were significantly higher than the rest group in the stage after Alzheimer's induction (p = 0.001). According to the results, it seems that aerobic exercise can help improve neuroplasticity in the hippocampus of Alzheimer's mice.

منابع و مأخذ:

1. Ahlskog, J.E., Geda, Y.E., Graff-Radford, N.R., Petersen, R.C., 2011. September. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. In Mayo Clinic Proceedings, 86(9): 876-884.


2. Barnes, D.E., Yaffe, K. 2011. The projected effect of risk factor reduction on Alzheimer's disease prevalence. The Lancet Neurology, 10(9): 819-828.


3. Barrientos, R.M., Sprunger, D.B., Campeau, S., Watkins, L. R., Rudy, J. W., Maier, S.F. 2004. BDNF mRNA expression in rat hippocampus following contextual learning is blocked by intrahippocampal IL-1beta administration. Journal of Neuroimmunology, 155(1-2): 119-126.


4. Cassilhas, R., Lee, K., Fernandes, J., Oliveira, M., Tufik, S., Meeusen, R., De Mello, M. 2012. Spatial memory is improved by aerobic and resistance exercise through divergent molecular mechanisms. Neuroscience, 202: 309-317.


5. Chae, C.H., Kim, H.T. 2009. Forced, moderate-intensity treadmill exercise suppresses apoptosis by increasing the level of NGF and stimulating phosphatidylinositol 3-kinase signaling in the hippocampus of induced aging rats. Neurochemistry International, 55(4): 208-213.


6. Chen, M.J., Russo‐Neustadt, A.A. 2009. Running exercise‐induced up‐regulation of hippocampal brain‐derived neurotrophic factor is CREB‐ Hippocampus, 19(10): 962-972.


7. Chennaoui, M., Drogou, C., Gomez-Merino, D. 2008. Effects of physical training on IL-1β, IL-6 and IL-1ra concentrations in various brain areas of the rat. European Cytokine Network, 19(1): 8-14.


8. Cysneiros, R.M., Ferrari, D., Arida, R.M., Terra, V.C., de Almeida, A.-C. G., Cavalheiro, E.A., Scorza, F.A. 2010. Qualitative analysis of hippocampal plastic changes in rats with epilepsy supplemented with oral omega-3 fatty acids. Epilepsy and Behavior, 17(1): 33-38.


9. 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.


10. Devan, B.D., Bowker, J.L., Duffy, K.B., Bharati, I.S., Jimenez, M., Sierra-Mercado, D., Ingram, D.K. 2006. Phosphodiesterase inhibition by sildenafil citrate attenuates a maze learning impairment in rats induced by nitric oxide synthase inhibition. Psychopharmacology, 183(4): 439-445.


11. Domek-Lopacinska, K.U., Strosznajder, J.B. 2010. Cyclic GMP and nitric oxide synthase in aging and Alzheimer's disease. Molecular Neurobiology, 41(2-3): 129-137.


12. Erickson, K.I., Voss, M.W., Prakash, R.S., Basak, C., Szabo, A., Chaddock, L,.White, S. M. 2011. Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences, 108(7): 3017-3022.


13. Farmer, J., Zhao, X., van Praag, H., Wodtke, K., Gage, F. H., Christie, B.R. 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.


14. García-Mesa, Y., Pareja-Galeano, H., Bonet-Costa, V., Revilla, S., Gómez-Cabrera, M. C., Gambini, J., Sanfeliu, C. 2014. Physical exercise neuroprotects ovariectomized 3xTg-AD mice through BDNF mechanisms. Psycho neuroendocrinology, 45: 154-166.


15. Gharari Arefi, R., Saghebjoo, M., Hedayati, M., and Fathi, R. 2016. The effect of aerobic training and omega-3 consumption on brain-derived neurotrophic factor in the hippocampus of male rats with homocysteine induced Alzheimer's disease. Scientific Journal of Kurdistan University of Medical Sciences, 21(2): 53-64.


16. Griffin, É. W., Mullally, S., Foley, C., Warmington, S. A., O'Mara, S. M., and Kelly, Á.M. 2011. Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males. Physiology and Behavior, 104(5): 934-941.


17. Hansson, O., Zetterberg, H., Buchhave, P., Andreasson, U., Londos, E., Minthon, L., and Blennow, K. 2007. Prediction of Alzheimer’s disease using the CSF Aβ42/Aβ40 ratio in patients with mild cognitive impairment. Dementia and Geriatric Cognitive Disorders, 23(5): 316-320.


18. Hosseinzadeh, S., Roshan, V.D., Pourasghar, M. 2013. Effects of intermittent aerobic training on passive avoidance test (shuttle box) and stress markers in the dorsal hippocampus of wistar rats exposed to administration of homocysteine. Iranian Journal of Psychiatry and Behavioral Sciences, 7(1): 37.


19. Kang, E. B., Cho, J.Y. 2014. Effects of treadmill exercise on brain insulin signaling and β-amyloid in intracerebroventricular streptozotocin induced-memory impairment in rats. Journal of Exercise Nutrition and Biochemistry, 18(1): 89.


20. Kang, E.B., Kwon, I.S., Koo, J.H., Kim, E.J., Kim, C.H., Lee, J. Cho, J.Y. 2013. Treadmill exercise represses neuronal cell death and inflammation during Abeta-induced ER stress by regulating unfolded protein response in aged presenilin 2 mutant mice. Apoptosis, 18(11): 1332-1347.


21. Lynch, M.A. 2004. Long-term potentiation and memory. Physiological Reviews, 84(1): 87-136.


22. Mangialasche, F., Solomon, A., Winblad, B., Mecocci, P., Kivipelto, M. 2010. Alzheimer's disease: clinical trials and drug development. The Lancet Neurology, 9(7): 702-716.


23. Morris, K.A., Gold, P.E. 2012. Age-related impairments in memory and in CREB and pCREB expression in hippocampus and amygdala following inhibitory avoidance training. Mechanisms of Ageing and Development, 133(5): 291-299.


24. Nichol, K.E., Poon, W.W., Parachikova, A.I., Cribbs, D.H., Glabe, C.G., Cotman, C. W. 2008. Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid. Journal of Neuroinflammation, 5: 13.


25. Pilc, J. (2010). The effect of physical activity on the brain derived neurotrophic factor: from animal to human studies. Journal of Physiology and Pharmacology, 61(5): 533-541.


26. Prickaerts, J., van Staveren, W. C., Sik, A., Markerink-van Ittersum, M., Niewohner, U., van der Staay, F. J., de Vente, J. 2002. Effects of two selective phosphodiesterase type 5 inhibitors, sildenafil and vardenafil, on object recognition memory and hippocampal cyclic GMP levels in the rat. Neuroscience, 113(2): 351-361.


27. Puzzo, D., Staniszewski, A., Deng, S. X., Privitera, L., Leznik, E., Liu, S., Arancio, O. 2009. Phosphodiesterase 5 inhibition improves synaptic function, memory, and amyloid-beta load in an Alzheimer's disease mouse model. Journal of Neuroscience, 29(25), 8075-8086.


28. Rockwood, K., and Middleton, L. 2007. Physical activity and the maintenance of cognitive function. Alzheimer's and Dementia, 3(2): S38-S44.


29. Stranahan, A. M., Lee, K., Becker, K. G., Zhang, Y., Maudsley, S., Martin, B., Mattson, M.P. 2010. Hippocampal gene expression patterns underlying the enhancement of memory by running in aged mice. Neurobiology of Aging, 31(11): 1937-1949.


30. Tong, L., Balazs, R., Thornton, P. L., and Cotman, C.W. 2004. β-amyloid peptide at sublethal concentrations downregulates brain-derived neurotrophic factor functions in cultured cortical neurons. Journal of Neuroscience, 24(30): 6799-6809.


31. Vilela, T.C., Muller, A. P., Damiani, A. P., Macan, T. P., da Silva, S., Canteiro, P. B., de Andrade, V. M. 2017. Strength and aerobic exercises improve spatial memory in aging rats through stimulating distinct neuroplasticity mechanisms. Molecular Neurobiology, 54(10): 7928-7937.


32. Wei, Z., Belal, C., Tu, W., Chigurupati, S., Ameli, N. J., Lu, Y., Chan, S. L. 2012. Chronic nicotine administration impairs activation of cyclic AMP-response element binding protein and survival of newborn cells in the dentate gyrus. Stem Cells and Development, 21(3): 411-422.


33. Zagaar, M., Alhaider, I., Dao, A., Levine, A., Alkarawi, A., Alzubaidy, M., Alkadhi, K. 2012. The beneficial effects of regular exercise on cognition in REM sleep deprivation: behavioral, electrophysiological and molecular evidence. Neurobiology of Disease, 45(3): 1153-1162.


34. Zare, M., Zar, A., Edalatmanesh, M. A. (2016). The Implementation of Eight Weeks of Endurance Training and Lithium Chloride Administration on Brain-Derived Neurotrophic Factor (BDNF) Serum Levels in Rats with Alzheimer's Disease. Journal of Advances in Medical and Biomedical Research, 24(103): 62-70.


35. Zhang, Y. Y., Fan, Y. C., Wang, M., Wang, D., Li, X. H. 2013. Atorvastatin attenuates the production of IL-1beta, IL-6, and TNF-alpha in the hippocampus of an amyloid beta1-42-induced rat model of Alzheimer's disease. Clinical Interventions in Aaging, 8: 103-110.