تأثیر 12 هفته تمرینات ورزشی هوازی بر روی رفتارهای افسردگی و سطوح هورمون‌های تستوسترون و کورتیکوسترون در رت‌های نر مبتلا به آلزایمر

نوع مقاله : مقاله پژوهشی Released under (CC BY-NC 4.0) license I Open Access I

نویسندگان

1 استادیار، گروه تربیت بدنی و علوم ورزشی، دانشگاه پیام نور، تهران، ایران

2 کارشناسی ارشد فیزیولوژی ورزشی، گروه فیزیولوژی ورزش، دانشگاه پیام نور، تهران، ایران

10.22049/jahssp.2021.27472.1399

چکیده

هدف: با توجه به نقشی که هورمون‌ها در میزان افسردگی ناشی از بیماری آلزایمر دارند و همچنین تاثیری که تمرینات ورزشی بر سطوح ترشح هورمون‌ها در بدن دارند، هدف از پژوهشحاضر بررسی تأثیر 12 هفته تمرینات ورزشی هوازی بر روی رفتارهای افسردگی و سطوح هورمون‌های تستوسترون و کورتیکوسترون در رت­های نر مبتلا به آلزایمر بود. روش شناسی: بدین منظور 40 سر رت نر ویستار با میانگین سنی 8 هفته‌ و با میانگین وزنی 33±237 گرم بطور تصادفی در چهار گروه 10 سری شامل: کنترل، ورزش، آلزایمر و ورزش +آلزایمر قرار گرفتند. برای القا آلزایمر، مقدار 3 میلی‌گرم بر کیلوگرم استرپتوزوتوسین در حجم 5 میکرولیتر آب مقطر استریل در ناحیه بطن مغز تزریق شد. پروتکل تمرینی به مدت 12 هفته، پنج جلسه در هفته و 30 دقیقه در هر جلسه با سرعت 10 متر بر دقیقه از هفته اول تا ششم و سرعت 12 متر بر دقیقه از هفته هفتم تا دوازدهم اجرا شد. در انتهای دوره تمرینی آزمون‌‌های ترجیح ساکارز و شنای اجباری به عنوان تست‌های برآورد افسردگی انجام شد. پس از تکمیل تست‌های رفتاری، اندازه‌گیری سطوح هورمون‌های تستوسترون و کورتیکوسترون به روش الایزا انجام شد. یافته‌ها: نتایج نشان داد که 12 هفته تمرینات ورزشی سبب کاهش معنی‌دار زمان بی‌تحرکی در تست شنای اجباری و افزایش معنی‌دار آزمون ترجیح ساکارز (001/0=P) در رت‌های مبتلا به آلزایمر شده است. همچنین یک دوره تمرینات ورزشی هوازی سبب افزایش معنی دار هورمون‌ تستوسترون (006/0=P) و کاهش معنی‌دار هورمون کورتیکوسترون (006/0=P) در رت‌های مبتلا به آلزایمر شده است. نتیجه‌گیری: به نظر می‌رسد که تمرین هوازی دویدن روی تردمیل، با افزایش سطوح تستوسترون و کاهش کورتیکوسترون بر رفتارهای مربوط به افسردگی در موش های صحرایی مبتلا به بیماری آلزایمر موثر بوده است.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

The effect of 12 weeks of aerobic exercise training on depressive behaviors, testosterone and corticosterone levels in rats with Alzheimer's

نویسندگان [English]

  • Saeed Naghibi 1
  • Ali Barzegari 1
  • Mozhgan Rostami 2
1 Assistant Professor, Department of physical education, Payame Noor University, Tehran, IRAN.
2 MSc, Department of physical education, Payame Noor University, PO BOX 19395-3697, Tehran, IRAN
چکیده [English]

Aim: Considering the role of hormones on depression's levels that caused by Alzheimer's disease, and also the effect of exercise training on hormone secretion levels in the body, the aim of this study was to investigate the effect of 12 weeks of aerobic exercise training on depressive behaviors and hormones levels of testosterone and corticosterone in Alzheimer's male rats. Methods: For this purpose, 40 male Wistar rats with an average age of 8 weeks and average weight of 237±33 g were randomly divided into four groups of 10: control, exercise, Alzheimer's and exercise + Alzheimer's. To induce Alzheimer's, 3 mg/kg streptozotocin in 5 μl of sterile distilled water was injected into the ventricular region. The training protocol was performed for 12 weeks, 5 sessions/week and 30 minutes in each session at a speed of 10 m/min from the first to the 6 weeks and 12 m/min from the 7 to the 12 weeks. At the end of the training period, Sucrose preference and forced swimming tests were performed as tests for estimating depression. After completing the behavioral tests, testosterone and corticosterone levels were measured by ELISA. Results: The results showed that 12 weeks of exercise training significantly reduced the immobility time in the forced swimming test (P = 0.001)  and significantly increased the sucrose preference test (P = 0.001) in rats with Alzheimer's disease. Also, a period of exercise training has caused a significant increase in testosterone (P = 0.006) and a significant decrease in corticosterone (P = 0.006) in rats with Alzheimer's disease. Conclusion: Aerobic exercise training on treadmill appears to be effective in treating depressive behaviors in rats with Alzheimer's disease by increasing testosterone levels and decreasing corticosterone.

کلیدواژه‌ها [English]

  • Alzheimer
  • Depression
  • Testosterone
  • Corticosterone
  • Aerobic exercise training

   

 

This is an open access article distributed under the following Creative Commons license: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

  1.  

    1. De la Rosa A, Olaso-Gonzalez G, Arc-Chagnaud C, Millan F, Salvador-Pascual A, García-Lucerga C, et al. Physical exercise in the prevention and treatment of Alzheimer's disease. Journal of Sport and Health Science. 2020;9(5):394-404.
    2. Yirmiya R, Goshen I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain, behavior, and immunity. 2011;25(2):181-213.
    3. Fernández M, Gobartt AL, Balañá M. Behavioural symptoms in patients with Alzheimer's disease and their association with cognitive impairment. BMC neurology. 2010;10(1):1-9.
    4. Nazem A, Sankowski R, Bacher M, Al-Abed Y. Rodent models of neuroinflammation for Alzheimer’s disease. Journal of neuroinflammation. 2015;12(1):1-15.
    5. Prasansuklab A, Tencomnao T. Amyloidosis in Alzheimer’s disease: the toxicity of amyloid beta (Aβ), mechanisms of its accumulation and implications of medicinal plants for therapy. Evidence-Based Complementary and Alternative Medicine. 2013;2013.
    6. Benilova I, Karran E, De Strooper B. The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes. Nature neuroscience. 2012;15(3):349-57.
    7. Gouras GK, Tampellini D, Takahashi RH, Capetillo-Zarate E. Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease. Acta neuropathologica. 2010;119(5):523-41.
    8. Rosario ER, Chang L, Stanczyk FZ, Pike CJ. Age-related testosterone depletion and the development of Alzheimer disease. Jama. 2004;292(12):1431-2.
    9. Emmelot-Vonk MH, Verhaar HJ, Pour HRN, Aleman A, Lock TM, Bosch JR, et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. Jama. 2008;299(1):39-52.
    10. Hasegawa N, Mochizuki M. Improved effect of Pycnogenol® on impaired spatial memory function in partial androgen deficiency rat model. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2009;23(6):840-3.
    11. Janowsky JS, Oviatt SK, Orwoll ES. Testosterone influences spatial cognition in older men. Behavioral neuroscience. 1994;108(2):325.
    12. Finsterwald C, Alberini CM. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies. Neurobiology of learning and memory. 2014;112:17-29.
    13. Yazdanshenas A, Peeri M, Azarbyjani M. The Effect of Voluntary Training on Testosterone and Corticosterone Levels in Male Rats Following Maternal Separation. The Horizon of Medical Sciences. 2018;24(4):316-23 [In Persian].
    14. Salvador A. Steroid hormones and some evolutionary-relevant social interactions. Motivation and Emotion. 2012;36(1):74-83.
    15. Walther A, Breidenstein J, Miller R. Association of testosterone treatment with alleviation of depressive symptoms in men: a systematic review and meta-analysis. JAMA psychiatry. 2019;76(1):31-40.
    16. Kheirkhah F, Hosseini SR, Hosseini SF, Ghasemi N, Bijani A, Cumming RG. Relationship between testosterone levels and depressive symptoms in older men in Amirkola, Iran. Caspian journal of internal medicine. 2014;5(2):65.
    17. Nandam LS, Brazel M, Zhou M, Jhaveri DJ. Cortisol and major depressive disorder—translating findings from humans to animal models and back. Frontiers in psychiatry. 2020;10:974.
    18. Lin T-W, Shih Y-H, Chen S-J, Lien C-H, Chang C-Y, Huang T-Y, et al. Running exercise delays neurodegeneration in amygdala and hippocampus of Alzheimer’s disease (APP/PS1) transgenic mice. Neurobiology of learning and memory. 2015;118:189-97.
    19. Babaei P, Azali Alamdari K, Soltani Tehrani B, Damirchi AJJSMPF. Effect of six weeks of endurance exercise and following detraining on serum brain derived neurotrophic factor and memory performance in middle aged males with metabolic syndrome. 2013;53(4):437-43.
    20. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, et al. Exercise training increases size of hippocampus and improves memory. Proceedings of the national academy of sciences. 2011;108(7):3017-22.
    21. Aras S, Tek I, Varli M, Yalcin A, Cengiz OK, Atmis V, et al. Plasma Viscosity: Is a Biomarker for the Differential Diagnosis of Alzheimer’s Disease and Vascular Dementia? American Journal of Alzheimer's Disease & Other Dementias®. 2013;28(1):62-8.
    22. Antunes H, De Mello M, Santos-Galduróz R, Galduróz J, Lemos VA, Tufik S, et al. Effects of a physical fitness program on memory and blood viscosity in sedentary elderly men. Brazilian Journal of Medical and Biological Research. 2015;48:805-12.
    23. Karkoulias K, Habeos I, Charokopos N, Tsiamita M, Mazarakis A, Pouli A, et al. Hormonal responses to marathon running in non-elite athletes. European Journal of Internal Medicine. 2008;19(8):598-601.
    24. Daly W, Seegers C, Rubin D, Dobridge J, Hackney A. Relationship between stress hormones and testosterone with prolonged endurance exercise. European journal of applied physiology. 2005;93(4):375-80.
    25. Tokmakidis SP, Spassis AT, Volaklis KA. Training, detraining and retraining effects after a water-based exercise program in patients with coronary artery disease. Cardiology. 2008;111(4):257-64.
    26. Hayes LD, Elliott BT. Short-term exercise training inconsistently influences basal testosterone in older men: a systematic review and meta-analysis. Frontiers in physiology. 2019;9:1878.
    27. Tsolakis CK, Vagenas GK, Dessypris AG. Strength adaptations and hormonal responses to resistance training and detraining in preadolescent males. The Journal of Strength & Conditioning Research. 2004;18(3):625-9.
    28. Safari MA, Koushkie Jahromi M, Rezaei R, Aligholi H, Brand S. The effect of swimming on anxiety-like behaviors and corticosterone in stressed and unstressed rats. International journal of environmental research and public health. 2020;17(18):6675.
    29. Sigwalt A, Budde H, Helmich I, Glaser V, Ghisoni K, Lanza S, et al. Molecular aspects involved in swimming exercise training reducing anhedonia in a rat model of depression. Neuroscience. 2011;192:661-74.
    30. Entezari Z, Babaei A, Rahmati-Ahmadabad S. Effect of Voluntary Exercise Training on Corticosterone Level and Immobility Behavior Induced by Chronic Stress in Rats. Caspian Journal of Neurological Sciences. 2020;6(3):164-9.
    31. Yuede CM, Zimmerman SD, Dong H, Kling MJ, Bero AW, Holtzman DM, et al. Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer's disease. Neurobiology of disease. 2009;35(3):426-32.
    32. Um HS, Kang EB, Cho IH, Kim CH, Cho JS, Hwang DY. The combination of exercise training and α-lipoic acid treatment has therapeutic effects on the pathogenic phenotypes of Alzheimer's disease in NSE/APPsw-transgenic mice. International journal of molecular medicine. 2010;25(3):337-46.
    33. Wolf SA, Kronenberg G, Lehmann K, Blankenship A, Overall R, Staufenbiel M, et al. Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer’s disease. Biological psychiatry. 2006;60(12):1314-23.
    34. Hosseinzadeh S, Dabidi Roshan V, Mahjoub S, Taghipour Darzi M. The interactive effect of lead acetate and endurance training on the brain-derived neurotrophic factor and malondialdehyde levels in rats cortex. Journal of babol university of medical sciences. 2012;14(2):7-15 [In Persian].
    35. Hosseinlou A, Pouzesh jadidi R, Azali Alamdari K, Bashiri J, Nourazar MAR. Effects of HIIT and curcumin consumption on brain lipid peroxidation, homocysteine and caspase activation in rats exposed to drinking water arsenic %J Journal of Practical Studies of Biosciences in Sport. 2021:-.
    36. Babaei P, damirchi a, Azali Alamdari K. Effects of Endurance Training and Detraining on Serum BDNF and Memory Performance in Middle Aged Males with Metabolic Syndrome %J Iranian Journal of Endocrinology and Metabolism. 2013;15(2):132-42.
    37. Naghibi S, Joneydi MS, Barzegari A, Davoodabadi A, Ebrahimi A, Eghdami E, et al. Treadmill exercise sex-dependently alters susceptibility to depression-like behaviour, cytokines and BDNF in the hippocampus and prefrontal cortex of rats with sporadic Alzheimer-like disease. Physiology & Behavior. 2021;241:113595.
    38. Wallace DL, Vialou V, Rios L, Carle-Florence TL, Chakravarty S, Kumar A, et al. The influence of ΔFosB in the nucleus accumbens on natural reward-related behavior. Journal of Neuroscience. 2008;28(41):10272-7.
    39. Cryan JF, Markou A, Lucki I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends in pharmacological sciences. 2002;23(5):238-45.
    40. Juszczyk G, Mikulska J, Kasperek K, Pietrzak D, Mrozek W, Herbet M. Chronic Stress and Oxidative Stress as Common Factors of the Pathogenesis of Depression and Alzheimer’s Disease: The Role of Antioxidants in Prevention and Treatment. Antioxidants. 2021;10(9):1439.
    41. Valenzuela PL, Castillo-García A, Morales JS, de la Villa P, Hampel H, Emanuele E, et al. Exercise benefits on Alzheimer’s disease: State-of-the-science. Ageing research reviews. 2020;62:101108.
    42. Khodadadi D, Gharakhanlou R, Naghdi N, Salimi M, Azimi SM, Shahed A. The effect of 4 weeks of exercise preconditioning on soluble amyloid beta level and memory impairment in rats with Alzheimer's disease induced by Aβ1-42 injection. Razi Journal of Medical Sciences. 2018;24(165):66-76 [In Persian].
    43. Radak Z, Toldy A, Szabo Z, Siamilis S, Nyakas C, Silye G, et al. The effects of training and detraining on memory, neurotrophins and oxidative stress markers in rat brain. Neurochemistry international. 2006;49(4):387-92.
    44. Um HS, Kang EB, Leem YH, Cho IH, Yang CH, Chae KR, et al. Exercise training acts as a therapeutic strategy for reduction of the pathogenic phenotypes for Alzheimer's disease in an NSE/APPsw-transgenic model. International journal of molecular medicine. 2008;22(4):529-39.
    45. Adlard PA, Perreau VM, Pop V, Cotman CW. Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease. Journal of Neuroscience. 2005;25(17):4217-21.
    46. Deslandes A, Moraes H, Ferreira C, Veiga H, Silveira H, Mouta R, et al. Exercise and mental health: many reasons to move. Neuropsychobiology. 2009;59(4):191-8.
    47. Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Abou Haidar E, Stringer T, et al. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. Elife. 2016;5:e15092.
    48. Kramer AF, Hahn S, Cohen NJ, Banich MT, McAuley E, Harrison CR, et al. Ageing, fitness and neurocognitive function. Nature. 1999;400(6743):418-9.
    49. Brzyska M, Elbaum D. Dysregulation of calcium in Alzheimer's disease. Acta neurobiologiae experimentalis. 2003;63(3):171-84.
    50. Larun L, Nordheim LV, Ekeland E, Hagen KB, Heian F. Exercise in prevention and treatment of anxiety and depression among children and young people. Cochrane database of systematic reviews. 2006(3).
    51. Ang E-T, Dawe GS, Wong PT, Moochhala S, Ng Y-K. Alterations in spatial learning and memory after forced exercise. Brain research. 2006;1113(1):186-93.
    52. Wong-Goodrich SJ, Pfau ML, Flores CT, Fraser JA, Williams CL, Jones LW. Voluntary running prevents progressive memory decline and increases adult hippocampal neurogenesis and growth factor expression after whole-brain irradiation. Cancer research. 2010;70(22):9329-38.
    53. García-Capdevila S, Portell-Cortés I, Torras-Garcia M, Coll-Andreu M, Costa-Miserachs D. Effects of long-term voluntary exercise on learning and memory processes: dependency of the task and level of exercise. Behavioural brain research. 2009;202(2):162-70.
    54. Snigdha S, De Rivera C, Milgram NW, Cotman C. Exercise enhances memory consolidation in the aging brain. Frontiers in aging neuroscience. 2014;6:3.
    55. Black SR, Goldstein BL, Klein DN. Parental depression moderates the relationships of cortisol and testosterone with children's symptoms. Journal of affective disorders. 2019;251:42-51.
    56. Frye CA, Edinger KL, Seliga AM, Wawrzycki JM. 5α-reduced androgens may have actions in the hippocampus to enhance cognitive performance of male rats. Psychoneuroendocrinology. 2004;29(8):1019-27.
    57. Verhovshek T, Cai Y, Osborne MC, Sengelaub DR. Androgen regulates brain-derived neurotrophic factor in spinal motoneurons and their target musculature. Endocrinology. 2010;151(1):253-61.
    58. Tan R. Memory loss as a reported symptom of andropause. Archives of andrology. 2001;47(3):185-9.
    59. Galea LA, Kavaliers M, Ossenkopp K-P, Hampson E. Gonadal hormone levels and spatial learning performance in the Morris water maze in male and female meadow voles, Microtus pennsylvanicus. Hormones and behavior. 1995;29(1):106-25.
    60. Goudsmit E, Van de Poll N, Swaab D. Testosterone fails to reverse spatial memory decline in aged rats and impairs retention in young and middle-aged animals. Behavioral and neural biology. 1990;53(1):6-20.
    61. Babai A, Salmani Nodoushan I, Babai S, Jahesh H, Dehnavieh R. The effect of one session of exhausting exercise in testosterone and progesterone of male runners. SSU_Journals. 2013;20(5):679-89 [In Persian].
    62. Radak Z, Chung HY, Koltai E, Taylor AW, Goto S. Exercise, oxidative stress and hormesis. Ageing research reviews. 2008;7(1):34-42.
    63. Riachy R, McKinney K, Tuvdendorj DR. Various factors may modulate the effect of exercise on testosterone levels in men. Journal of Functional Morphology and Kinesiology. 2020;5(4):81.
    64. Ida M, Ida I, Wada N, Sohmiya M, Tazawa M, Shirakura K. A clinical study of the efficacy of a single session of individual exercise for depressive patients, assessed by the change in saliva free cortisol level. BioPsychoSocial medicine. 2013;7(1):1-11.
    65. Babaei A, Nourshahi M, Jameie SB, Fayaz Milani R, Haghparast A. The Protective Effect of Interval and Continuous Exercise Training on Corticosterone, Weight Gain and Behavioral Despair in Rats Following a Period of Chronic Unpredictable Stress. Sport Physiology. 2018;10(39):75-86 [In Persian].
    66. Flood JF, Vidal D, Bennett EL, Orme AE, Vasquez S, Jarvik ME. Memory facilitating and anti-amnesic effects of corticosteroids. Pharmacology Biochemistry and Behavior. 1978;8(1):81-7.
    67. Dominique J-F, Roozendaal B, McGaugh JL. Stress and glucocorticoids impair retrieval of long-term spatial memory. Nature. 1998;394(6695):787-90.
    68. Ramamoorthy S, Cidlowski JA. Corticosteroids: mechanisms of action in health and disease. Rheumatic Disease Clinics. 2016;42(1):15-31.