مقایسه اثر دو شیوه تمرین اختیاری در محیط غنی سازی شده و تمرین اجباری بر بیان Wnt-5a و تجمع آمیلوئید بتا در بافت هیپوکامپ موشهای مبتلا به دیابت نوع 3

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، پردیس البرز دانشگاه تهران، تهران، ایران

2 گروه فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه تهران، تهران، ایران

چکیده

مقدمه و هدف: دیابت نوع 3 یا دیابت مغزی اصطلاحی است برای بیماری آلزایمر که مقاومت انسولینی مغز را به طور انتخابی درگیر وسبب کاهش شناخت وحافظه می شود. مسیر سیگنالینگ Wnt  در سیستم عصبی، کاهش علائم بیماری آلزایمر، سنتز انسولین و دیابت نقش دارد. اگرچه تأثیر مثبت فعالیتهای بدنی در بیماری‌ها گزارش شده است، اما مقایسه نوع تمرینات کمتر مورد بررسی قرار گرفته است. هدف از پژوهش حاضر مقایسه اثر تمرین اختیاری در محیط غنی سازی شده و تمرین اجباری بر بیان پروتئین Wnt-5a و آمیلوئیدبتا (Aβ) در بافت هیپوکامپ موشهای دیابت نوع 3 می‌باشد.
مواد و روش ها: 25 سر موش به 5 گروه کنترل سالم، شم، دیابت 3، دیابت 3 + تمرین اختیاری در محیط غنی و دیابت 3 + تمرین اجباری تقسیم شدند. القای دیابت 3 با تزریق استروپتوزوسین داخل بطنی و تائید مدل با آزمون رفتاری صورت گرفت. پروتکل تمرینی طی هشت هفته اجرا شد. بیان پروتئین  Wnt-5aبه روش وسترن بلات و تجمع Aβ با رنگ آمیزی تیوفلاوین S انجام شد. تحلیل داده با آزمون آنالیز واریانس یک­ سویه وآزمون تعقیبی توکی صورت گرفت (05/0P≤).
نتایج: تمرین اجباری و اختیاری سبب افزایش معنادار در بیان پروتئین Wnt-5a شد (05/0P≤). در مقایسه گروههای تمرینی، Wnt-5a در موشهای محیط غنی افزایش بیشتری داشت. تجمع Aβ در هر دو گروه تمرینی در مقایسه با گروه دیابت 3 کاهش معناداری یافت (05/0P≤) که این کاهش در محیط غنی بیشتر بود.
نتیجه‌گیری: تمرینات اجباری و اختیاری با فعال کردن مسیر سیگنالینگ Wnt/β-catenin در مغز باعث کاهش تجمع پلاکهای Aβ گردید. به نظر می‌رسد محیط غنی تأثیر بهتری در کاهش علائم مبتلایان دیابت نوع 3 در مقایسه با تمرین اجباری دارد که احتمالاً ناشی از کاهش عوامل استرس‌زا بر مغز باشد.

کلیدواژه‌ها

عنوان مقاله [English]

Comparison of the effect of voluntary exercise in enriched environment and forced exercise on Wnt-5a expression and Amyloid Beta accumulation in hippocampus of rats with type 3 diabetes

نویسندگان [English]

  • Sanaz Zanjanian 1
  • Mohammad Reza Kordi 2
  • Ali Asghar Ravasi 2
1 Department of Exercise Physiology, Faculty of Physical Education, Alborz Campus, University of Tehran, Tehran, Iran
2 Department of Exercise Physiology, Faculty of Physical Education, University of Tehran, Tehran, Iran
چکیده [English]

Background and Objective: Type 3 diabetes or brain diabetes is a term for Alzheimer, which insulin resistance selectively affects brain and causes cognitive loss. Wnt signaling pathways play role in nervous system, reducing symptoms of Alzheimer's disease, insulin synthesis and diabetes. Although positive effect of physical activities in diseases has been reported, the comparison of types of exercises has been less investigated. The aim of this study was to compare the effect of voluntary in an enriched environment and forced exercise on Wnt-5a expression and Aβ in hippocampus of type3 diabetic rats.
Materials and Methods: 25 rats were divided into 5 groups: healthy control, sham, diabetes3, diabetes3+voluntary exercise in rich environment, diabetes3+forced exercise. Type3 diabetes was induced by intraventricular injection of streptozocin and the model was confirmed by behavioral test. The protocol was done during eight weeks. Wnt-5a expression was done by western blot method and Aβ accumulation was done by thioflavin S staining. Data analysis was done by ANOVA and Tukey's post hoc test (P≤0.05).
Results: Two exercise group had a significant increase in expression of Wnt-5a in hippocampus (P≤0.05). In the comparison between exercise groups, the expression of Wnt-5a increased more in rich environment rats. The accumulation of Aβ in exercise groups was significantly reduced (P≤0.05) compared to the type 3 diabetes group, which was greater in the rich environment.
Conclusion: Forced and voluntary exercises by activating Wnt/β-catenin pathway in brain reduced accumulation of Aβ plaques. Rich environment has better effect in reducing the symptoms of patients compared to forced exercise, which may be due to reduced stressors in brain.

کلیدواژه‌ها [English]

  • Type 3 diabetes
  • High intensity interval
  • Rich environment
  • Wnt-5a
  • Amyloid Beta

مراجع

  1. Chen XQ, Mobley WC. Alzheimer disease pathogenesis: insights from molecular and cellular biology studies of oligomeric Aβ and tau species. Frontiers in Neuroscience 2019;13:659.
  2. Justice NJ. The relationship between stress and Alzheimer's disease. Neurobiology of Stress 2018;8:127-133.
  3. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Ostolaza H, Martín C. Pathophysiology of Type 2 Diabetes Mellitus. International Journal of Molecular Sciences 2020;21(17):6275.
  4. Pugazhenthi S, Qin L, Reddy PH. Common neurodegenerative pathways in obesity, diabetes, and Alzheimer's disease. Biochemistry and Molecular Genetics of Disease Processes and Models of Human Disease Journal 2017;1863(5):1037-1045.
  5. Kandimalla R, Thirumala V, Reddy PH. Is Alzheimer's disease a Type 3 Diabetes? A critical appraisal. Biochemistry and Molecular Genetics of Disease Processes and Models of Human Disease Journal 2017;1863(5):1078-1089.
  6. Folch J, Ettcheto M, Busquets O, Sánchez-López E, Castro-Torres RD, Verdaguer E, et al. The Implication of the Brain Insulin Receptor in Late Onset Alzheimer's Disease Dementia. Pharmaceuticals Journal (Basel) 2018;11(1):11.
  7. Rad SK, Arya A, Karimian H, et al. Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: link between type 2 diabetes and Alzheimer's disease. Journal of Drug Design, Development and Therapy 2018;12:3999-4021.
  8. Nguyen TT, Ta QT, Nguyen TK, Nguyen TT, Van Giau V. Type 3 Diabetes and its role Implications in Alzheimer's Disease. International Journal of Molecular Sciences 2020;21(9):3165.
  9. Michailidis M, Moraitou D, Tata DA, Kalinderi K, Papamitsou T, Papaliagkas V. Alzheimer's disease as type 3 diabetes: Common pathophysiological mechanisms between Alzheimer’s disease and type 2 diabetes. International Journal of Molecular Sciences 2022;23(5):2687.
  10. Stanganello E, Zahavi EE, Burute M, Smits J, Jordens I, Maurice MM, et al. Wnt signaling directs neuronal polarity and axonal growth. Journal of Science 2019;13:318-327.
  11. Arredondo SB, Valenzuela-Bezanilla D, Mardones MD, Varela-Nallar L. Role of Wnt Signaling in Adult Hippocampal Neurogenesis in Health and Disease. Journal Frontiers in Cell and Developmental Biology 2020;8:860
  12. Wisniewska MB. Physiological role of β-catenin/TCF signaling in neurons of the adult brain. Neurochemical Research 2013;38(6):1144-55.
  13. Palomer E, Buechler J, Salinas PC. Wnt Signaling Deregulation in the Aging and Alzheimer's Brain. Journal of Frontiers Cell Neuroscience 2019;13:227
  14. Tapia-Rojas C, Inestroza NC. Loss of canonical Wnt signaling is involved in the pathogenesis of Alzheimer's disease. Journal of Neural Regeneration Research 2018;13(10):1705.
  15. Chen CM, Orefice LL, Chiu SL, LeGates TA, Hattar S, Huganir RL, Zhao H, Xu B, Kuruvilla R. Wnt-5ais essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice. Journal of Proceedings of the National Academy of Sciences 2017;114(4):619-28.
  16. Sebastian B. Arredondo, Fernanda G. Guerrero, Andrea Herrera-Soto, Joaquin Jensen-Flores, Daniel B. Bustamante, Alejandro Oñate-Ponce, Pablo Henny. Wnt5a promotes differentiation and development of adult-born neurons in the hippocampus by noncanonical Wnt signaling, Stem Cells 2022;38(3):422–436
  17. Simonetti M, Kuner R. Spinal Wnt5a Plays a Key Role in Spinal Dendritic Spine Remodeling in Neuropathic and Inflammatory Pain Models and in the Proalgesic Effects of Peripheral Wnt3-a. Journal of Neuroscience 2020;40(35):6664-6677.
  18. Xiong X, Shao W, Jin T. New insight into the mechanisms underlying the function of the incretin hormone glucagon-like peptide-1 in pancreatic β-cells: the involvement of the Wnt signaling pathway effector β-catenin. Journal of Islets 2012;4(6):359-65.
  19. Costa R, Peruzzo R, Bachmann M, Montà GD, Vicario M, Santinon G, et al. Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction. Journal of Cell Reports 2019;28(8):1949-1960.
  20. Chen M, Do H. Wnt Signaling in Neurogenesis during Aging and Physical Activity. Journal of Brain Science 2012;2(4):745-68.
  21. Mahmoudi Y, Gholami M, Nikbakht H, Ebrahim K, Bakhtiyari S. Effect of high intensity interval training with metformin on lipid profiles and HbA1c in diabetic rats. The Iranian Journal of Diabetes and Obesity (IJDO) 2018;10(3):144-150.
  22. Zheng L,Rao Z, GuoY, Chen P, Xiao W. High-Intensity Interval Training Restores Glycolipid Metabolism and Mitochondrial Function in Skeletal Muscle of Mice With Type 2 Diabetes. Front Endocrinol (Lausanne) 2020;11:561.
  23. Yang D, Yang Y, Li Y, Han R. Physical exercise as therapy for type 2 diabetes mellitus: from mechanism to orientation. Annals of Nutrition and Metabolism 2019;74:313-321.
  24. Kim DY, Jung SY, Kim K, Kim CJ. Treadmill exercise ameliorates Alzheimer disease-associated memory loss through the Wnt signaling pathway in the streptozotocin-induced diabetic rats. Journal of Exercise Rehabilitation 2016;12(4):276-83.
  25. Naderi S, Habibi A, Kesmati M, Rezaie A, Ghanbarzadeh M. The effects of six weeks high intensity interval training on Amyloid Beta1-42 Peptide in Hippocampus of Rat Model of Alzheimer’ s Disease Induced with STZ. Journal of Clinical Research in Paramedical Sciences 2018;7(2).
  26. Rahimi Saghand M, Rajabi H, Dehkhoda M, Hosseini A. The Effects of eight weeks high-intensity interval training vs. continuous moderate-intensity training on plasma Dickkopf-1 and glycemic control in patients with type 2 diabetes. Annals of Applied Sport Science Journal 2020;8(2).
  27. Mora F. Successful brain aging: plasticity, environmental enrichment, and lifestyle. Journal of Dialogues in Clinical Neuroscience 2013;15(1):45-52.
  28. Jin X, Li T, Zhang L, Ma J, Yu L, Li C, Niu L. Environmental enrichment improves spatial learning and memory in vascular dementia rats with activation of Wnt/β-catenin signal pathway. Journal of Medical Science Monitor 2017;23:207-215.
  29. Pamidi N, Nayak S. Effect of environmental enrichment exposure on neuronal morphology of streptozotocin-induced diabetic and stressed rat hippocampus. Biomedical Journal 2014;37(4):225-231.
  30. Zhang X, Shi X, Wang J, Xu Z, He J. Enriched environment remedies cognitive dysfunctions and synaptic plasticity through NMDAR-Ca2+-Activin A circuit in chronic cerebral hypoperfusion rats. Journal of Aging (Albany NY) 2021;13(16):20748-20761.
  31. Leon M, Woo C. Environmental Enrichment and Successful Aging. Front Behavior Neuroscience 2018;12:155.
  32. Kamat PK. Streptozotocin induced Alzheimer's disease like changes and the underlying neural degeneration and regeneration mechanism. Neural Regeneration Research Journal 2015;10(7):1050-2
  33. . Bromley-Brits K, Deng Y, Song W. Morris water maze test for learning and memory deficits in Alzheimer's disease model mice. Journal of Visualized Experiments 2011;20(53):2920.
  34. Wang N, Liu Y, Ma Y, Wen D. High-intensity interval versus moderate-intensity continuous training: Superior metabolic benefits in diet-induced obesity mice. Life Science Journal 2017;191:122-131.
  35. Li B, Liang F, Ding X, Yan Q, Zhao Y, Zhang X et al. Interval and continuous exercise overcome memory deficits related to β-Amyloid accumulation through modulating mitochondrial dynamics. Behavioural Brain Research 2019;376: 112171.
  36. Herring A, Blome M, Ambrée O, Sachser N, Paulus W, Keyvani K. Reduction of cerebral oxidative stress following environmental enrichment in mice with Alzheimer-like pathology. Brain Pathology Journal 2010;20(1):166-75.
  37. Lin, CM, Chen, HH, Lin, CA. et al. Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling. Science Report 2017;7:372.
  38. Christensen A, Pike CJ. Staining and Quantification of β-Amyloid Pathology in Transgenic Mouse Models of Alzheimer's Disease. Methods Molecular Biology Journal 2020;2144:211-221.
  39. Vorhees CV, Williams M T. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nature Protocols 2006:1(2):848-858.
  40. de Sousa Fernandes, Ordônio TF, Santos GCJ, Santos LER, Calazans CT, Gomes DA, Santos TM. Effects of Physical Exercise on Neuroplasticity and Brain Function: A Systematic Review in Human and Animal Studies. Neural Plast 2020;2020:8856621.
  41. Riahi S, Riyahi F, Yaribeygi H. Diabetes and Role of Exercise on its Control; A systematic Review. Health Research Journal Baqiyatallah  2016;1 (2):113-121. 
  42. Narendra Pamidi, Christina Gertrude Yap, Sathha Nayak B. Protective effect of environmental enrichment on the morphology of neurons in the motor cortex of diabetic and stressed rats. Archives of Biochemistry and Molecular Biology 2019;10:052-070.
  43. Yoon JC, Ng A, Kim BH, Bianco A, Xavier RJ, Elledge SJ. Wnt signaling regulates mitochondrial physiology and insulin sensitivity. Genes & Developmen 2010;24(14):1507-18.
  44. Clemenson, G. D., Gage, F. H., & Stark, C. E. Environmental enrichment and neuronal plasticity. The Oxford Handbook of Developmental Neural Plasticity 2018; 85:283-284.
  45. Li B, Liang F, Ding X, Yan Q, Zhao Y, Zhang X, et al. Interval and continuous exercise overcome memory deficits related to β-Amyloid accumulation through modulating mitochondrial dynamics. Behavioral Brain Research Journal 2019; 376:112171.
  46. Prado Lima MG, Schimidt HL, Garcia A, Daré LR, Carpes FP, Izquierdo I, et al. Environmental enrichment and exercise are better than social enrichment to reduce memory deficits in Amyloid beta neurotoxicity. Proceedings of the National Academy of Sciences of the United States of America (PNAS) Journal 2018;115(10):2403-2409.
  47. Ball NJ, Mercado III E, Orduña I. Enriched environments as a potential treatment for developmental disorders: A Critical Assessment. Frontiers in Psychology 2019;10:466.
  48. Robison LS, Francis N, Popescu DL, Anderson ME, Hatfield J, Xu F, et al. Environmental enrichment: disentangling the influence of novelty, social, and physical activity on cerebral amyloid angiopathy in a transgenic mouse model. International Journal of Molecular Sciences 2020;21(3):843.
  49. Birch AM, McGarry NB, Kelly AM. Short-term environmental enrichment, in the absence of exercise, improves memory, and increases NGF concentration, early neuronal survival, and synaptogenesis in the dentate gyrus in a time-dependent manner. Hippocampus Journal 2013;23(6):437-50.
  50. Singhal G, Morgan J, Jawahar MC, Corrigan F, Jaehne EJ, Toben C, et al. Short-term environmental enrichment, and not physical exercise, alleviate cognitive decline and anxiety from middle age onwards without affecting hippocampal gene expression. Cognitive, Affective, & Behavioral Neuroscience Journal 2019;19(5):1143-1169.
  51. Rostami, S, Haghparast A, Fayazmilani R. The effect of combined training and play in an enriched environment during pre-pubertal period on hippocampal structure of adult rats. Sport Physiology Journal 2021;13(49):199-222.
  52. Fabel K, Wolf SA, Ehninger D, Babu H, Leal-Galicia P, Kempermann G. Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice. Frontiers Neuroscience 2009;3:50.
  53. Orellana AM, Vasconcelos AR, Leite JA, de Sá Lima L, Andreotti DZ, Munhoz CD, et al. Age-related neuroinflammation and changes in AKT-GSK-3β and Wnt/ β-Catenin signaling in rat hippocampus. Aging (Albany NY) 2015;7(12):1094-1100.
  54. Lee CB, Baek SS. Impact of exercise on hippocampal neurogenesis in hyperglycemic diabetes. Journal of Exercise Rehabilitation 2020;16(2):115-117.
  55. Fujimaki S, Kuwabara T. Diabetes-Induced Dysfunction of Mitochondria and Stem Cells in Skeletal Muscle and the Nervous System. International Journal of Molecular Sciences 2017;18(10):2147.
  56. Scheibner K, Bakhti M, Bastidas-Ponce A, Lickert H. Wnt signaling: Implications in endoderm development and pancreas organogenesis. Current Opinion in Cell Biology 2019;61:48-55.
  57. Yang Q, Wang WW, Ma P, Ma ZX, Hao M, Adelusi TI, et al. Swimming training alleviated insulin resistance through Wnt3a/β-catenin signaling in type 2 diabetic rats. Iran Journal of Basic Medical Science 2017;20(11):1220-1226.
  58. Zhou L, Chen D, Huang XM, Long F, Cai H, Yao WX, et all. Wnt5a Promotes Cortical Neuron Survival by Inhibiting Cell-Cycle Activation. Frontiers in Cellular Neuroscience 2017;11:281.
  59. Kimura LF, Novaes LS, Picolo G, Munhoz CD, Cheung CW, Camarini R. How environmental enrichment balances out neuroinflammation in chronic pain and comorbid depression and anxiety disorders. Brain Journal Pharmacology 2022;179(8):1640-1660.
  60. Pamidi N, Yap CG, Nayak S. Environmental enrichment preserves hippocampal neurons in diabetes and stressed rats. Histology & Histopathology 2022;37(4):385-395.

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