تأثیر شش هفته تمرین تناوبی شدید بر بیان ژن و محتوای پروتئین‌های KIF5B و Dynein در هیپوکمپ موش‌های صحرایی نر ویستار

نوع مقاله: مقاله پژوهشی

نویسندگان

1 دانشجوی دکتری فیزیولوژی ورزشی، گروه تربیت بدنی و علوم ورزشی دانشکدۀ ادبیات و علوم انسانی دانشگاه لرستان، خرم‌آباد، ایران

2 استادیار گروه تربیت بدنی و علوم ورزشی دانشکدۀ ادبیات و علوم انسانی دانشگاه لرستان، خرم‌آباد، ایران

3 دانشیار گروه تربیت بدنی و علوم ورزشی دانشکدۀ ادبیات و علوم انسانی دانشگاه لرستان، خرم‌‌آباد، ایران

4 دانشیار گروه تربیت بدنی و علوم ورزشی دانشکدۀ ادبیات و علوم انسانی دانشگاه ولی‌عصر ( عج) رفسنجان، رفسنجان، ایران

چکیده

 
انتقال سیتوپلاسمی فرایندی حیاتی در دستگاه عصبی است که موجب بهبود بقای عصبی می‌شود. پروتئین‌های KIF5B و Dynein موتورهای حرکتی درگیر در انتقال سیتوپلاسمی هستند که نقش مهمی در انتقال رو به ­جلو و عقب محموله‌های مختلف دارند، اما تأثیر تمرینات ورزشی به‌ویژه تمرین تناوبی شدید (HIIT) بر بیان این پروتئین­ها کمتر بررسی شده است. ازاین‌رو در این پژوهش، تأثیر HIIT بر بیان ژن و میزان پروتئین‌های KIF5B و Dynein در هیپوکمپ موش‌های صحرایی نر ویستار بررسی شد. آزمودنی‌های پژوهش شامل 14 سر موش بود که به دو گروه تمرین (7) و کنترل (7) تقسیم شدند. برنامۀ تمرینی به مدت شش هفته و هر هفته پنج جلسه بر روی نوار گردان انجام گرفت. برای بررسی میزان پروتئین KIF5B و Dynein از روش ایمونوهیستوشیمی و برای اندازه‌گیری بیان mRNA متغیرهای پژوهش از روش Real-Time PCR استفاده شد. یافته‌های پژوهش نشان داد که شش هفته HIIT به کاهش معنا‌داری در بیان ژن KIF5B و Dynein (به‌ترتیب 001/0 P= و 001/0 P= و درصد تغییرات=072/-) منجر شد. همچنین در پی انجام شش هفته تمرین، کاهش معنا‌داری در محتوای KIF5B (001/0P=) و Dynein (004/0P=) مشاهده شد. این یافته‌ها بیانگر این مطلب است که HIIT با تنظیم کاهشی بیان ژن و محتوای پروتئینی KIF5B و Dynein در بافت هیپوکمپ مرتبط است، هرچند سازوکارهای پایه ناشناخته باقی مانده‌اند. این تغییرات نشان می‌دهد که HIIT ممکن است بر انتقال سیتوپلاسمی روبه‌جلو و روبه­عقب تأثیر منفی داشته باشد، چراکه انتقال سیتوپلاسمی به‌وسیلۀ KIF5B و Dynein میانجی‌گری می‌شود.

کلیدواژه‌ها


عنوان مقاله [English]

The Effect of 6 Weeks of High Intensity Interval Training on the Gene Expression and Content of KIF5B and Dynein Proteins in Hippocampus of Male Wistar Rats

نویسندگان [English]

  • Hadi Kerendi 1
  • Rahim Mirnasoori 2
  • Masoud Rahmati 3
  • Abdolreza Kazemi 4
1 Ph.D. Student in Exercise Physiology, Department of Physical Education and Sport Sciences, Faculty of Literature and Humanities, Lorestan University, Khorramabad, Iran
2 Assistant Professor, Department of Physical Education and Sport Sciences, Faculty of Literature and Humanities, Lorestan University, Khorramabad, Iran
3 Associate Professor, Department of Physical Education and Sport Sciences, Faculty of Literature and Humanities, Lorestan University, Khorramabad, Iran
4 Associate Professor, Department of Physical Education and Sport Sciences, Faculty of Literature and Humanities, Vali-E-Asr University of Rafsanjan, Rafsanjan, Iran
چکیده [English]

Cytoplasmic transport is a vital process in the CNS that improves neuronal survival. KIF5B and Dynein are motor proteins involved in cytoplasmic transport which play an important role in the anterograde/retrograde transport. However, the effect of training especially high intensity interval training (HIIT) is less clear on the expression of these proteins. The present study examined the effect of HIIT on the gene expression and the amount of KIF5B and Dynein proteins in the hippocampal tissue of Wistar male rats. 14 rats were divided into 2 groups: (1) the training (TG: n=7) and (2) the control (CG: n=7). Training program was carried out on a treadmill for 6 weeks, 5 sessions per week. The protein contents of KIF5B and Dynein were determined by the immunohistochemical analysis. Moreover, the Real-Time polymerase chain reaction (Real-Time PCR) procedure was used to measure mRNA expression of the variables. The findings showed that 6 weeks of HIIT significantly decreased the gene expression of KIF5B and Dynein (P=0.001 and P=0.001 or percentage of changes= -0.72 respectively). Also, HIIT significantly decreased KIF5B (P=0.001) and Dynein (P=0.004) protein content after 6 weeks of HIIT. These findings demonstrated that HIIT was associated with the down-regulation of gene expression and protein content of KIF5B and Dynein in the hippocampal tissue although the underlying mechanisms have remained unknown. These changes show that HIIT may have negative effects on anterograde/retrograde cytoplasmic transport because the cytoplasmic transport is mediated by KIF5B and Dynein.

کلیدواژه‌ها [English]

  • Dynein
  • HIIT
  • KIF5B
  • Cytoplasmic Transport
  • Hippocampus

1.  DEPARTMENTdl A. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY-PART B: BIOCHEMISTRY & MOLECULAR BIOLOGY. 1976.

2.  Saxton WM, Hollenbeck PJ. The axonal transport of mitochondria. J Cell Sci. 2012;125(9):2095-104.

3.  LaMonte BH, Wallace KE, Holloway BA, Shelly SS, Ascaño J, Tokito M, et al. Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron. 2002;34(5):715-27.

4.  Hirokawa N, Niwa S, Tanaka Y. Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease. Neuron. 2010;68(4):610-38.

5.  Guo ZH, Mattson MP. Neurotrophic factors protect cortical synaptic terminals against amyloidand oxidative stress-induced impairment of glucose transport, glutamate transport and mitochondrial function. Cereb Cortex. 2000;10(1):50-7.

6.  Martin M, Iyadurai SJ, Gassman A, Gindhart JG, Hays TS, Saxton WM. Cytoplasmic dynein, the dynactin complex, and kinesin are interdependent and essential for fast axonal transport. Mol Biol Cell. 1999;10(11):3717-28.

7.  Cai Q, Pan P-Y, Sheng Z-H. Syntabulin–kinesin-1 family member 5B-mediated axonal transport contributes to activity-dependent presynaptic assembly. J Neurosci. 2007;27(27):7284-96.

8.  Chan J, Huang J, Lai K, editors. The Kinesin motor protein KIF5B regulates RNA trafficking and dendritic spine morphogenesis in hippocampal neuron. Neuroscience Symposium & Annual Scientific Conference of the Hong Kong Society of Neurosciences; 2016: The University of Hong Kong.

9.  Nitta R, Hirokawa N. Kinesin: Fundamental properties and structure. Encyclopedia of Biophysics: Springer; 2013. p. 1183-91.

10. Hirokawa N, Noda Y, Tanaka Y, Niwa S. Kinesin superfamily motor proteins and intracellular transport. Nat Rev Mol Cell Biol. 2009; 10(10):682-96.

11. Lin Y. Kif5b may play a role in impairing mouse memory: a behaviour and cellular study [postgraduate thesis]. The University of Hong Kong (Pokfulam, Hong Kong): The University of Hong Kong; 2013.

12. Argyropoulos G, Stütz AM, Ilnytska O, Rice T, Teran-Garcia M, Rao D, et al. KIF5B gene sequence variation and response of cardiac stroke volume to regular exercise. physiolgenomics. 2009;36(2):79-88.

13. Baptista FI, Pinto MJ, Elvas F, Almeida RD, Ambrósio AF. Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus. PloS one. 2013;8(6):e65515.

14. Kapitein LC, Schlager MA, Kuijpers M, Wulf PS, van Spronsen M, MacKintosh FC, et al. Mixed microtubules steer dynein-driven cargo transport into dendrites. Curr Biol. 2010;20(4):290-9.

15. Ross JL, Wallace K, Shuman H, Goldman YE, Holzbaur EL. Processive bidirectional motion of dynein–dynactin complexes in vitro. Nat Cell Biol. 2006;8(6):562-70.

16. Grabham PW, Seale GE, Bennecib M, Goldberg DJ, Vallee RB. Cytoplasmic dynein and LIS1 are required for microtubule advance during growth cone remodeling and fast axonal outgrowth. J Neurosci. 2007;27(21):5823-34.

17. Heerssen HM, Pazyra MF, Segal RA. Dynein motors transport activated Trks to promote survival of target-dependent neurons. Nat Neurosci. 2004;7(6):596-604.

18. Terada S, Hirokawa N. Moving on to the cargo problem of microtubule-dependent motors in neurons. Curr Opin Neurobiol. 2000;10(5):566-73.

19. Vallee RB, Williams JC, Varma D, Barnhart LE. Dynein: An ancient motor protein involved in multiple modes of transport. J Neurobiol. 2004;58(2):189-200.

20. Johnston JA, Illing ME, Kopito RR. Cytoplasmic dynein/dynactin mediates the assembly of aggresomes. Cell Motil Cytoskeleton. 2002;53(1):26-38.

21. Maday S, Wallace KE, Holzbaur EL. Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons. J Cell Biol. 2012;196(4):407-17.

22. Olton DS, Walker JA, Gage FH. Hippocampal connections and spatial discrimination. Brain Res. 1978;139(2):295-308.

23. Morris R, Garrud P, Rawlins J, O'Keefe J. Place navigation impaired in rats with hippocampal lesions. Nature. 1982;297(5868):681-3.

24. Wirth M, Madison CM, Rabinovici GD, Oh H, Landau SM, Jagust WJ. Alzheimer's disease neurodegenerative biomarkers are associated with decreased cognitive function but not β-amyloid in cognitively normal older individuals. J Neurosci. 2013;33(13):5553-63.

25. Bavelier D, Neville HJ. Cross-modal plasticity: where and how? Nat Rev Neurosci. 2002;3(6):443-52.

26. Becker S, Wojtowicz JM. A model of hippocampal neurogenesis in memory and mood disorders. Trends Cogn Sci. 2007;11(2):70-6.

27. McEwen BS. Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Ann N Y Acad Sci. 2001;933(1):265-77.

28. Arida RM, Scorza CA, Scorza FA, da Silva SG, da Graça Naffah-Mazzacoratti M, Cavalheiro EA. Effects of different types of physical exercise on the staining of parvalbumin-positive neurons in the hippocampal formation of rats with epilepsy. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(4):814-22.

29. Huttenlocher PR. Neural plasticity: Harvard University Press; 2009.

30. Kleim JA, Jones TA. Principles of experience-dependent neural plasticity: implications for rehabilitation after brain damage. J Speech Lang Hear Res. 2008;51(1):S225-S39.

31. Vaynman S, Gomez-Pinilla F. License to run: exercise impacts functional plasticity in the intact and injured central nervous system by using neurotrophins. Neurorehabil Neural Repair. 2005;19(4):283-95.

32. Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002;25(6):295-301.

33. Van Praag H. Neurogenesis and exercise: past and future directions. Neuromolecular Med. 2008;10(2):128-40.

34. Van Praag H, Shubert T, Zhao C, Gage FH. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci. 2005;25(38):8680-5.

35. Radák Z, Sasvári M, Nyakas C, Taylor AW, Ohno H, Nakamoto H, et al. Regular training modulates the accumulation of reactive carbonyl derivatives in mitochondrial and cytosolic fractions of rat skeletal muscle. Arch Biochem Biophys. 2000;383(1):114-8.

36. Shokouhi G, Tubbs R, Shoja M, Roshangar L, Mesgari M, Ghorbanihaghjo A, et al. The effects of aerobic exercise training on the age-related lipid peroxidation, Schwann cell apoptosis and ultrastructural changes in the sciatic nerve of rats. Life Sci. 2008;82(15-16):840-6.

37. Aguiar A, Boemer G, Rial D, Cordova F, Mancini G, Walz R, et al. High-intensity physical exercise disrupts implicit memory in mice: involvement of the striatal glutathione antioxidant system and intracellular signaling. Neuroscience. 2010;171(4):1216-27.

38. Nytrøen K, Rustad LA, Aukrust P, Ueland T, Hallén J, Holm I, et al. High‐Intensity Interval Training Improves Peak Oxygen Uptake and Muscular Exercise Capacity in Heart Transplant Recipients. Am J Transplant. 2012;12(11):3134-42.

39. Gillen JB, Percival ME, Skelly LE, Martin BJ, Tan RB, Tarnopolsky MA, et al. Three minutes of all-out intermittent exercise per week increases skeletal muscle oxidative capacity and improves cardiometabolic health. PLoS One. 2014;9(11):e111489.

40. Laursen PB, Jenkins DG. The scientific basis for high-intensity interval training. Sports Med. 2002;32(1):53-73.

41. Afzalpour ME, Chadorneshin HT, Foadoddini M, Eivari HA. Comparing interval and continuous exercise training regimens on neurotrophic factors in rat brain. Physiol Behav. 2015;147:78-83.

42. de Almeida AA, da Silva SG, Fernandes J, Peixinho-Pena LF, Scorza FA, Cavalheiro EA, et al. Differential effects of exercise intensities in hippocampal BDNF, inflammatory cytokines and cell proliferation in rats during the postnatal brain development. Neurosci Lett. 2013;553:1-6.

43. Winter B, Breitenstein C, Mooren FC, Voelker K, Fobker M, Lechtermann A, et al. High impact running improves learning. Neurobiol Learn Mem. 2007;87(4):597-609.

44. Aguiar AS, Speck AE, Prediger RD, Kapczinski F, Pinho RA. Downhill training upregulates mice hippocampal and striatal brain-derived neurotrophic factor levels. J Neural Transm. 2008;115(9):1251-5.

45. McLaughlin S. EXERCISE ENHANCES ALLOCENTRIC PROCESSING AND HIPPOCAMPAL FUNCTION IN THE ADULT BRAIN 2016.

46. Aguiar AS, Tuon T, Pinho CA, Silva LA, Andreazza AC, Kapczinski F, et al. Mitochondrial IV complex and brain neurothrophic derived factor responses of mice brain cortex after downhill training. Neurosci Lett. 2007;426(3):171-4.

47. Aguiar AS, Tuon T, Pinho CA, Silva LA, Andreazza AC, Kapczinski F, et al. Intense exercise induces mitochondrial dysfunction in mice brain. Neurochem Res. 2008;33(1):51-8.

48. Scopel D, Fochesatto C, Cimarosti H, Rabbo M, Belló-Klein A, Salbego C, et al. Exercise intensity influences cell injury in rat hippocampal slices exposed to oxygen and glucose deprivation. Brain Res Bull. 2006;71(1):155-9.

49. Rahmati M, Gharakhanlou R, Movahedin M, Mowla SJ, Khazani A, Fouladvand M, et al. Treadmill Training Modifies KIF5B Moter Protein in the STZ-induced Diabetic Rat Spinal Cord and Sciatic Nerve. Archives of Iranian Medicine (AIM). 2015;18(2).

50. Hafstad AD, Boardman NT, Lund J, Hagve M, Khalid AM, Wisløff U, et al. High intensity interval training alters substrate utilization and reduces oxygen consumption in the heart. J Appl Physiol. 2011;111(5):1235-41.

51. Kohler I, Meier R, Busato A, Neiger-Aeschbacher G, Schatzmann U. Is carbon dioxide (CO2) a useful short acting anaesthetic for small laboratory animals? Lab Anim. 1999;33(2):155-61.

52. Pfaffl MW. A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res. 2001;29(9):e45-e.

53. Cotman CW, Engesser-Cesar C. Exercise enhances and protects brain function. Exerc Sport Sci Rev. 2002;30(2):75-9.

54. Knaepen K, Goekint M, Heyman EM, Meeusen R. Neuroplasticity—exercise-induced response of peripheral brain-derived neurotrophic factor. Sports Med. 2010;40(9):765-801.

55. Hill RD, Storandt M, Malley M. The impact of long-term exercise training on psychological function in older adults. J Gerontol. 1993;48(1):P12-P7.

56. Dishman RK, Berthoud HR, Booth FW, Cotman CW, Edgerton VR, Fleshner MR, et al. Neurobiology of exercise. obesity. 2006;14(3):345-56.

57. Camiletti‐Moirón D, Aparicio V, Aranda P, Radak Z. Does exercise reduce brain oxidative stress? A systematic review. Scand J Med Sci Sports. 2013;23(4):e202-e12.

58. Kohman RA, Bhattacharya TK, Wojcik E, Rhodes JS. Exercise reduces activation of microglia isolated from hippocampus and brain of aged mice. J Neuroinflammation. 2013;10(1):114.

59. Cotman CW, Berchtold NC, Christie L-A. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007;30(9):464-72.

60. Hughes PE, Alexi T, Walton M, Williams CE, Dragunow M, Clark RG, et al. Activity and injury-dependent expression of inducible transcription factors, growth factors and apoptosis-related genes within the central nervous system. Prog Neurobiol. 1999;57(4):421-50.

61. Lou S-j, Liu J-y, Chang H, Chen P-j. Hippocampal neurogenesis and gene expression depend on exercise intensity in juvenile rats. Brain Res. 2008;1210:48-55.

62. Brisswalter J, Collardeau M, René A. Effects of acute physical exercise characteristics on cognitive performance. Sports Med. 2002;32(9):555-66.

63. Dietrich A, Audiffren M. The reticular-activating hypofrontality (RAH) model of acute exercise. Neurosci Biobehav Rev. 2011;35(6):1305-25.

64. Mekari S, Fraser S, Bosquet L, Bonnéry C, Labelle V, Pouliot P, et al. The relationship between exercise intensity, cerebral oxygenation and cognitive performance in young adults. Eur J Appl Physiol. 2015;115(10):2189-97.

65. Ogonovszky H, Berkes I, Kumagai S, Kaneko T, Tahara S, Goto S, et al. The effects of moderate-, strenuous-and over-training on oxidative stress markers, DNA repair, and memory, in rat brain. Neurochem Int. 2005;46(8):635-40.

66. Secher NH, Quistorff B. Brain glucose and lactate uptake during exhaustive exercise. J Physiol. 2005;568(1):3.

67. Inoue K, Hanaoka Y, Nishijima T, Okamoto M, Chang H, Saito T, et al. Long-term mild exercise training enhances hippocampus-dependent memory in rats. Int J Sports Med. 2015;36(04):280-5.

68. Inoue K, Okamoto M, Shibato J, Lee MC, Matsui T, Rakwal R, et al. Long-term mild, rather than intense, exercise enhances adult hippocampal neurogenesis and greatly changes the transcriptomic profile of the hippocampus. PLoS One. 2015;10(6):e0128720.

69. Oomen CA, Mayer JL, De Kloet ER, Joëls M, Lucassen PJ. Brief treatment with the glucocorticoid receptor antagonist mifepristone normalizes the reduction in neurogenesis after chronic stress. Eur J Neurosci. 2007;26(12):3395-401.

70. Smith MA, Makino S, Kvetnansky R, Post RM. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci. 1995;15(3):1768-77.

71. Schaaf MJ, de Jong J, de Kloet ER, Vreugdenhil E. Downregulation of BDNF mRNA and protein in the rat hippocampus by corticosterone. Brain Res. 1998;813(1):112-20.

72. Kuipers S, Trentani A, Den Boer J, Ter Horst G. Molecular correlates of impaired prefrontal plasticity in response to chronic stress. J Neurochem. 2003;85(5):1312-23.

73. Bhambhani Y, Malik R, Mookerjee S. Cerebral oxygenation declines at exercise intensities above the respiratory compensation threshold. Respir Physiol Neurobiol. 2007;156(2):196-202.

74. Head BP, Patel HH, Tsutsumi YM, Hu Y, Mejia T, Mora RC, et al. Caveolin-1 expression is essential for N-methyl-D-aspartate receptor-mediated Src and extracellular signal-regulated kinase 1/2 activation and protection of primary neurons from ischemic cell death. FASEB J. 2008;22(3):828-40.

75. Yamamoto M, Toya Y, Schwencke C, Lisanti MP, Myers MG, Ishikawa Y. Caveolin is an activator of insulin receptor signaling. J Biol Chem. 1998;273(41):26962-8.