ورزش و علوم زیست حرکتی

ورزش و علوم زیست حرکتی

بررسی اثر یک دوره تمرینات شنای تناوبی شدید بر بیان ژن LRRK2 و mir-205 موش‌های مبتلا به پارکینسون

نوع مقاله : مقاله پژوهشی

نویسندگان
1 دانشجوی دکتری فیزیولوژی ورزشی، گروه علوم ورزشی، دانشکده هنر و معماری، واحد شیراز، دانشگاه آزاد اسلامی، شیراز، ایران.
2 دانشیار فیزیولوژی ورزشی، گروه علوم ورزشی، دانشکده هنر و معماری، واحد شیراز، دانشگاه آزاد اسلامی، شیراز، ایران.
3 دانشیار فیزیولوژی جانوری، گروه زیست‌شناسی، دانشکده کشاورزی و علوم پایه، واحد شیراز، دانشگاه آزاد اسلامی، شیراز، ایران.
4 استادیار فیزیولوژی ورزشی، گروه علوم ورزشی، دانشکده هنر و معماری، واحد شیراز، دانشگاه آزاد اسلامی، شیراز، ایران.
چکیده
مقدمه و هدف: اختلال در miRNAها می‌تواند موجب بروز و پیشرفت بیماری‌هایی از جمله پارکینسون شود. اثر فعالیت‌های ورزشی بر عوامل مؤثر در پیشرفت بیماری پارکینسون و miRNA های مرتبط با آن به درستی مشخص نیست. هدف مطالعه حاضر بررسی اثر یک دوره تمرینات شنای تناوبی شدید بر بیان ژن LRRK2 و mir-205 موش‌های مبتلا به پارکینسون بود.
مواد و روش‌ها: تعداد 14 سر موش نر صحرایی نژاد ویستار 8 تا 10 هفته‌ای با تزریق روزانه 1 میلی‌گرم به ازای هر کیلوگرم وزن بدن ماده رزرپین و به مدت 5 روز به پارکینسون مبتلا شدند. سپس موش‌ها به طور تصادفی در دو گروه تمرین شنا و کنترل بیمار قرار گرفتند. 7 سرموش نیز بدون تزریق رزرپین به عنوان گروه سالم کنترل در نظر گرفته شد. موش‌های گروه تمرین، به مدت شش هفته و در قالب 20 نوبت 30 ثانیه‌ای با 30 ثانیه استراحت بین هر نوبت تمرینات شنا را اجرا کردند. پس از 48 ساعت از آخرین جلسه تمرینی، حیوانات کشتار و بیان ژن هیپوکامپی LRRK2 و mir-205 اندازه‌گیری شد. برای تجزیه و تحلیل اطلاعات از آزمون تحلیل واریانس یک راهه و در سطح معنی‌داری 0.05>P بهره گرفته شد.
یافته‌ها: بیان ژن LRRK2 در گروه بیمار نسبت به گروه کنترل سالم و گروه تمرین به طور معنی‌داری بالاتر بود (به ترتیب 0.001=P و 0.001=P) اما تفاوت معنی‌داری بین گروه تمرین و کنترل سالم مشاهده نشد (0.1=P). بیان ژن mir-205 در گروه بیمار نسبت به گروه سالم و گروه تمرین به طور معنی‌داری پایین‌تر بود (به ترتیب 0.001=P و 0.01=P). ارتباط معکوس و معنی‌داری بین بیان ژن هیپوکامپی LRRK2 و mir-205 مشاهده شد (0.01=P و 0.71-=r).
بحث و نتیجه‌گیری: به نظر می‌رسد تمرین شنای تناوبی شدید می‌تواند با کاهش بیان ژن LRRK2 و افزایش بیان ژن mir-205 در بهبود بیماری پارکینسون مؤثر باشد.
کلیدواژه‌ها

عنوان مقاله English

The effect of high intensity interval swimming on LRRK2 and mir-205 gene expression in rats with Parkinson’s disease

نویسندگان English

Somayeh Rashidfard 1
Mehrzad Moghadasi 2
Mohammdamin Edalatmanesh 3
Sara Hojati 4
1 PhD Student in Exercise Physiology, Department of Sport Science, Faculty of Art and Architecture, Shiraz branch, Islamic Azad University, Shiraz, Iran
2 Associate professor in Exercise Physiology, Department of Sport Science, Faculty of Art and Architecture, Shiraz branch, Islamic Azad University, Shiraz, Iran
3 Associate Professor in Animal Physiology, Department of biology, Faculty of Agriculture and Sciences, Shiraz branch, Islamic Azad University, Shiraz, Iran
4 Assistant Professor in Exercise Physiology, Department of Sport Science, Faculty of Art and Architecture, Shiraz branch, Islamic Azad University, Shiraz, Iran.
چکیده English

Introduction and Purpose: Dysregulation of miRNAs will result in development and progression of numerous diseases, such as in Parkinson’s disease (PD). The effect of exercise training on mechanisms of development and progression of PD are not well known. The aim of present study was to examine the effect of high intensity interval swimming on LRRK2 and mir-205 gene expression in rats with PD.
Materials and Methods: PD induced in fourteen 8 to 10-week-old male Wistar rats by injection of 1 mg/kg reserpine during 5 days. Then, these rats were divided into PD group or training group. Seven rats were considered as the healthy control group without any reserpine injection. The rats in the training group performed high intensity interval swimming, including 20 times of 30 seconds of swimming with 30 seconds of rest between each time for 6 weeks. 48h after last session of training, sacrificed animals and hypocampic LRKK2 and mir-205 gene expression was measured. To analyze data, the statistical method of one-way analysis of variance was used with significance P<0.05.
Results: The results indicated that LRRK2 gene expression were higher in the PD group compare to the healthy group and training group (P=0.001 and P=0.001 respectively) and no significant difference was observed between training group and healthy group (P=0.1). mir-205 gene expression was lower in the PD group compare to the healthy group and training group (P=0.001 and P=0.01 respectively). There was negative correlation between hypocampic LRKK2 and mir-205 gene expression (r=-0.71 and P=0.01).
Discussion and Conclusion: It seems that high intensity interval swimming improves PD by reducing LRRK2 and increasing mir-205 gene expression.

کلیدواژه‌ها English

High intensity interval swimming
Parkinson’s disease
LRRK2
mir-205
Wang W, Li J, Tao L, Lv L, Sun J, Zhang T, et al. MiR-205 regulates LRRK2 expression in dopamine neurons
in Parkinson's disease through methylation modification. Iranian Journal of Public Health. 2022; 51(7): 1637-
1647. https://doi.org/10.18502/ijph.v51i7.10098.
2. Belvisi D, Pellicciari R, Fabbrini A, Costanzo M, Pietracupa S, De Lucia M, et al. Risk factors of Parkinson
disease: Simultaneous assessment, interactions, and etiologic subtypes. Neurology. 2020; 95: e2500-e2508.
doi: 10.1212/WNL.0000000000010813.
3. Hardy J, Cai H, Cookson MR, Gwinn-Hardy K, Singleton A. Genetics of Parkinson's disease and
parkinsonism. Annals of Neurology. 2006;60:389–398. DOI: 10.1002/ana.21022.
4. Lesage S, Lunati A, Houot M, Romdhan SB, Clot F, Tesson C, et al. Characterization of recessive Parkinson
disease in a large multicenter study. Annals of Neurology. 2020; 88: 843–850. doi: 10.1002/ana.25787.
5. Tolosa E, Botta-Orfila T, Morato X, Calatayud C, Ferrer-Lorente R, Marti MJ, et al. MicroRNA alterations in
iPSC-derived dopaminergic neurons from Parkinson disease patients. Neurobiology of Aging. 2018; 69: 283–
291. doi: 10.1016/j.neurobiolaging.2018.05.032.
6. Alegre-Abarrategui J, Ansorge O, Esiri M, Wade-Martins R. LRRK2 is a component of granular alphasynuclein pathology in the brainstem of Parkinson's disease. Neuropathology and Applied Neurobiology, 2008;
34: 272-283. doi: 10.1111/j.1365-2990.2007.00888.x.
7. Rohani M. Genetics of Parkinson disease. Genetics in the Third Millennium. 2010; 8(1):1990-1997. [In
Persian].
8. Rui Q, Ni H, Li D, Gao R, Chen G. The Role of LRRK2 in neurodegeneration of Parkinson disease. Current
Neuropharmacology. 2018; 16(9): 1348–1357. doi: 10.2174/1570159X16666180222165418.
9. Kielb S, Kisanuki YY, Dawson E. Neuropsychological profile associated with an alpha-synuclein gene
(SNCA) duplication. Clinical Neuropsychologist. 2021; 36 (7): 1787-1798. https://doi.org/10. 1080/
13854046. 2021.1914735.
10. Vetchinova AS, Kapkaeva MR, Ivanov MV, Kutukova KA, Mudzhiri NM, Frumkina LE, et al. Mitochondrial
dysfunction in dopaminergic neurons derived from patients with LRRK2- and SNCA-associated genetic forms
of Parkinson’s disease. Current Issues in Molecular Biology. 2023; 45: 8395–8411. https://doi.org/10.3390/
cimb45100529.
11. O’Brien J, Hayder H, Zayed Y, Peng, C. Overview of microRNA biogenesis, mechanisms of actions, and
circulation. Frontiers Endocrinology. 2018; 9: 402. doi: 10.3389/fendo.2018.00402.
12. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with
antisense complementarity to lin-14. Cell. 1993; 75: 843–854. doi: 10.1016/0092-8674(93)90529-Y.
13. Hebert SS, De Strooper B. Alterations of the microRNA network cause neurodegenerative disease. Trends in
Neurosciences. 2009; 32: 199–206. doi: 10.1016/j.tins.2008.12.003.
14. Song H, Bu G. MicroRNA-205 inhibits tumor cell migration through downregulating the expression of the
LDL receptor-related protein 1. Biochemical and Biophysical Research Communications. 2009; 388: 400-405.
doi: 10.1016/j.bbrc.2009.08.020.
15.Cho HJ, Liu G, Jin SM, Parisiadou L, Xie C, Yu J, et al. MicroRNA-205 regulates the expression of Parkinson's
disease-related leucine-rich repeat kinase 2 protein. Human Molecular Genetic. 2013; 22(3): 608–620. doi:
10.1093/hmg/dds470.
16. Nies YH, Mohamad Najib NH, Lim WL, Kamaruzzaman MA, Yahaya MF, Teoh SL. MicroRNA
dysregulation in Parkinson’s disease: A narrative review. Frontiers Endocrinology. 2021; 15: https://doi.org/
10.3389/ fnins.2021. 660379.
17.Ji L, Steffens DC, Wang L. Effects of physical exercise on the aging brain across imaging modalities: a metaanalysis of neuroimaging studies in randomized controlled trials. International Journal of Geriatric
Psychiatry. 2021; 36: 1148–1157. doi: 10.1002/gps.5510 Epub 2021 Mar 5.
18. Sacheli MA, Neva JL, Lakhani B, Murray DK, Vafai N, Shahinfard E, et al. Exercise increases caudate
dopamine release and ventral striatal activation in Parkinson’s disease. Movement Disorders. 2019; 34: 1891–
1900. doi: 10.1002/mds.27865 Epub 2019 Oct 4.
19. Winner B, Melrose HL, Zhao C, Hinkle KM, Yue M, Kent C, et al. Adult neurogenesis and neurite outgrowth
are impaired in LRRK2 G2019S mice. Neurobiology of Disease. 2011; 41(3): 706–716. doi: 10.1016/j.nbd.
2010.12.008.
20. Schootemeijer S, Coker D, Shelton JF, Chanoff E, Rowbotham HM, Darweesh SKL, et al. Exercise
knowledge, barriers and motivators among LRRK2 G2019S mutation carriers. Parkinsonism & Related
Disorders. 2023; 113: 105497. doi: 10.1016/j.parkreldis.2023.105497.
21. Olson J, Sheean P, Matthews L, Chitambar CR, Banerjee A, Visotcky A, et al. Circulating miRNAs as early
indicators of diet and physical activity response in women with metastatic breast cancer. Future Science OA.
2021; 7(4): FSO694. doi: 10.2144/fsoa-2020-0208.
22.Rezaei Z, Shakerian S, Nikbakht M. Comparison of the effect of 10 weeks of high intensity interval training
with continuous endurance training on MiR-205 and VEGF gene expression in mice with breast cancer.
Journal of Applied Health Studies in Sport Physiology. 2019; 6(1): 37-44. [In Persian] http://dx.doi.org/
10.22049/jassp.2019.26611.1258.
23. Zahraei H, Mogharnasi M, Afzalpour ME, Fanaei H. The effect of 8 weeks of continuous and high intensity
interval swimming on chemerin levels in liver and visceral fat tissues and insulin resistance in male rats with
metabolic syndrome. Journal of Sport and Exercise Physiology. 2022; 15(1): 33-44. [In Persian].
[https://doi.org/10.52547/ joeppa.15.1.33.
24. Nagle EF, Sanders ME, Franklin BA. Aquatic high intensity interval training for cardiometabolic health:
Benefits and training design. American Journal of Lifestyle Medicine. 2017; 11(1): 64-76. https://doi:10.1177/
1559827615583640.
25. Khalaj A, Ahmadi R. The effect of treadmill exercise on catalepsy from reserpine-induced Parkinson model
in diabetic male rat. KAUMS Journal (FEYZ). 2016;20(5):397-404. [In Persian]
26. Hubrecht RC, Kirkwood J. The UFAW handbook on the care and management of laboratory and other research
animals: John Wiley & Sons; 2010.
27. Abbasi M, Kordi M, Daryanoosh F. The effect of eight weeks of high-intensity interval swimming training on
the expression of PGC-1α and IL-6 proteins and memory function in brain hippocampus in rats with nonalcoholic steatohepatitis induced by high fat diet. Journal of Applied Health Studies in Sport Physiology. 2023.
In press. doi: 10.22049/jahssp.2023.28611.1552.
28. Artzi M, Even-Sapir E, Shacham HL, Thaler A, Urterger AO, Bressman S, et al. DaT-SPECT assessment
depicts dopamine depletion among asymptomatic G2019S LRRK2 mutation carriers. PLoS One. 2017; 12:
e0175424. https://doi.org/10.1371/journal.pone.0175424.
29. Kluss JH, Mamais A, Cookson MR. LRRK2 links genetic and sporadic Parkinson's disease. Biochemical
Society Transaction. 2019: 47(2): 651-661. https://doi.org/10.1042/BST20180462.
30.Rocha EM, Keeney MR, Di Maio R, De Miranda BR, Greenamyre GT. LRRK2 and idiopathic Parkinson’s
disease. Trends in Neurosciences. 2022; 45(3): 224-236. https://doi.org/10.1016/j.tins.2021.12.002
31.Chen CY, Weng YH, Chien KY, Lin KJ, Yeh TH, Cheng YP, et al. (G2019S) LRRK2 activates MKK4-JNK
pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD. Cell Death
and Differentiation. 2012;19(10):1623–1633. http://dx.doi.org/10.1038/cdd.2012.42.
32.Ruffmann C, Giaccone G, Canesi M, Bramerio M, Goldwurm S, Gambacorta M, et al. Atypical tauopathy in
a patient with LRRK2-G2019S mutation and tremor-dominant Parkinsonism. Neuropathology and Applied
Neurobiology. 2012;38(4):382–386. http://dx.doi.org/10.1111/j.1365-2990.2011. 01216.x.
33. Li S, Bi G, Han S, Huang R. MicroRNAs play a role in Parkinson’s disease by regulating microglia function:
From pathogenetic involvement to therapeutic potential. Frontiers in Molecular Neuroscience.
2022;14:744942. https://doi.org/10.3389/fnmol.2021.744942.
34. Fletcher AM, Heaford AC, Trask DK. Detection of metastatic head and neck squamous cell carcinoma using
the relative expression of tissue-specific mir-205. Translational Oncology. 2008; 1:202–208. doi:
10.1593/tlo.08163.
35. Wu H, Mo YY. Targeting miR-205 in breast cancer. Expert Opinion on Therapeutic Targets. 2009;13:1439–
1448. doi: 10.1517/14728220903338777.
36. Patil KS, Basak I, Pal R, Ho HP, Alves G, Chang EJ, et al. A proteomics approach to investigate miR-153-3p
and miR-205-5p targets in neuroblastoma cells. PLoS One. 2015;10(12):e0143969. doi: 10.1371/journal.
pone.0143969.
37. Tiwari PC, Pal R. The potential role of neuroinflammation and transcription factors in Parkinson disease.
Dialogues in Clinical Neuroscience. 2017;19(1):71–80. doi: 10.31887/DCNS.2017.19.1/rpal.
38. Malczynska-Sims P, Chalimoniuk M, Wronski Z, Marusiak J, Sulek A. High-intensity interval training
modulates inflammatory response in Parkinson's disease. Aging Clinical and Experimental Research.
2022;34(9):2165-2176. doi: 10.1007/s40520-022-02153-5.

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