The effect of high intensity interval swimming training on Glial cell line-derived neurotrophic factor and Rearranged during transfection (RET) gene expression in hippocampal tissue in rats with reserpine induced-Parkinson's disease

Document Type : Original Article

Authors

1 Department of Sports Sciences, Shiraz Branch, Islamic Azad University, Shiraz, Iran

2 Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran

Abstract

Background and Purpose: Parkinson’s disease is a progressive neurological disorder, where loss of dopamine neurons in the substantia nigra and dopamine depletion in the striatum cause characteristic motor and nonmotor symptoms. Glial cell line-derived neurotrophic factor (GDNF) is one of the most important neurotrophins that regenerates dopaminergic neurons by Rearranged during transfection (RET) receptor tyrosine kinase in Parkinson's disease. The effect of exercise on these proteins are not well known. Therefore, the present study was conducted to examine the effect of high intensity swimming training on GDNF and RET gene expression in hippocampal tissue in rats with Parkinson's disease.
Material and Methods: In this experimental and pure study, twenty-one male Wistar rats (age 8 to 10 weeks and weight 200-250 gr) were purchased from the Animal Breeding Center of Islamic Azad University, Shiraz branch and transferred to the animal laboratory of this university. Parkinson's disease was induced in fourteen rats by injection of 1 mg/kg reserpine during 5 days. Thereafter, they were randomly divided into Parkinson's disease group or Parkinson’s disease + training group. The rats in the training group performed 6 weeks of high intensity interval swimming including 20 repetitions of 30 seconds swimming followed by 30 seconds rest. Moreover, seven remaining rats received no intervention and were allocated into the healthy control group. GDNF and RET gene expressions were measured in hippocampus 48h after the last training session, using Real Time-PCR. Data were analyzed by using one-way ANOVA test and Bonferoni’s post-hoc. Data were analyzed by using SPSS22 at the P<0.05.
Results: Data analyzes revealed that GDNF and RET gene expression were reduced after induction of Parkinson's disease compared to the healthy control group (P=0.001, P=0.03, respectively).After 6 weeks of training, GDNF and RET gene expressions were increased compared to the Parkinson's disease group (P=0.009, and P=0.007, respectively), whereas, no significant differences were observed between training group and healthy control group (P=0.6 and P=0.9. respectively).
Conclusion: In general, it seems that high-intensity interval swimming training used in this study could improve dopaminergic neuron survival in Parkinson's disease by increasing GDNF as a neurotrophine factor and subsequent signaling receptor tyrosine kinase RET. Since, the available data are scars in this field, future studies specially in human are needed.
 

Keywords


  1. Renko J, Mahato AK, Visnapuu T, Valkonen K, Karelson M, Voutilainen MH, et al. Neuroprotective potential of a small molecule RET agonist in cultured dopamine neurons and hemiparkinsonian rats. Journal of Parkinsons Dis 2021;11(3):1023-1046.
  2. Kalia LV, Lang AE. Parkinson’s disease. Lancet. 2015; 386: 896–912.
  3. Kravitz AV, Freeze BS, Parker PRL, Kay K, Thwin MT, Deisseroth K, et al. Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature. 2010; 466: 622–626.
  4. Burke RE, O’Malley K. Axon degeneration in Parkinson’s disease. Experimental Neurology. 2013; 246: 72–83.
  5. Skaper SD. The neurotrophin family of neurotrophic factors: an overview. Methods in Molecular Biology. 2012; 846: 1–12.
  6. Peterson AL, Nutt JG, Treatment of Parkinson's disease with trophic factors. Neurotherapeutics; 2008: 5: 270 –280.
  7. Paratcha G, Ledda F. GDNF and GFRalpha: a versatile molecular complex for developing neurons. Trends in Neurosciences. 2008; 31: 384–391.
  8. Conway JA, Ince S, Black S, Kramer GDNF/RET signaling in dopamine neurons in vivo. Cell and Tissue Research. 2020; 382(1): 135-146.
  9. Drinkut A, Tillack K, Meka DP, Schulz JB, Kügler S, Kramer Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in a Parkinson disease mouse model. Cell Death & Diseases. 2016; 7: e2359.
  10. Houghton FM, Adams SE, Ríos AS, Masino L, Purkiss AG, Briggs Architecture and regulation of a GDNF-GFRα1 synaptic adhesion assembly. Nature Communications. 2023; 20;14(1): 7551.
  11. Jafarian M, Alipour M. Modulatory effect of glial-derived growth factor on addiction. Shafaye Khatam; 2016; 4(4): 116-122. [In Persian]
  12. Kramer ER, Liss GDNF–Ret signaling in midbrain dopaminergic neurons and its implication for Parkinson disease. FEBS Letters. 2015; 589 (24): 3760-3772.
  13. Tomlinson L, Leiton CV, Colognato H. Behavioral experiences as drivers of oligodendrocyte lineage dynamics and myelin plasticity. Neuropharmacology. 2016; 110: 548-62.
  14. Gyorkos AM, McCullough MJ, Spitsbergen J. Effect of varying exercise intensities on GDNF expression and neuromuscular junction morphology. The FASEB Journal. 2012; 26(S1): 1086.14-1086.14.
  15. McCullough MJ, Gyorkos AM, Johna MS. Short-term exercise increases GDNF protein levels in spinal cord of young and old rats. 2013; 240: 258–268.
  16. Cintron-Colon A, Spitsbergen J. Effect of long-term exercise on GDNF expression and innervation in rat skeletal muscle. The FASEB Journal. 2019; 33(S1): 700.25-700.25.
  17. Samadian Z, Tofighi A, Razi M, Ghaderi Pakdel F, Tolouei Azar Effect of moderate-intensity exercise training on GDNF signaling pathway in testicles of rats after experimental diabetes type 1 induction. Diabetes Research and Clinical Practice. 2020; 167:108332.
  18. Karimi M, Kaki A. The effect of aerobic exercise with melatonin on GDNF gene expression and some indicators of oxidative stress in male rats with diabetic neuropathic pain. Daneshvar Medicine 2021; 29(3):132-146.
  19. Abadian F, Fallahmohammadi Z. Neuroprotective Effect of Voluntary Wheel Running Exercise on GDNF levels of Cerebellum in Parkinsonian Rats. Journal of Sport and Exercise Physiology. 2012; 10:753-759. [In Persian]
  20. 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]
  21. Bayati M, Gharakhanlou R, Farzad B. Adaptations of physiological performance following high-intensity interval training. Sport Physiol. 2015; 7:15-32. [In Persian]
  22. Nagle EF, Sanders ME, Franklin BA. Aquatic high intensity interval training for cardiometabolic health: Benefits and training design. Am J Lifestyle Med. 2017; 11(1): 64-76.
  23. 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.
  24. Hubrecht R, Kirkwood J. UFAW Handbook on the care and management of laboratory and other research animals. 8th ed. Wiley-Blackwell Publishing Ltd; 2010; 460-520.
  25. 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 non-alcoholic steatohepatitis induced by high fat diet. Journal of Applied Health Studies in Sport Physiology. 2023; In press
  26. Park JS, Davis RL, Sue CM. Mitochondrial dysfunction in Parkinson’s disease: new mechanistic insights and therapeutic perspectives. Current Neurology and Neuroscience Reports. 2018; 18:21.
  27. Gantner CW, de Luzy IR, Kauhausen JA, Moriarty N, Niclis JC, Bye CR, et al. Viral delivery of GDNF promotes functional integration of human stem cell grafts in Parkinson’s disease. Cell Stem Cell, 2020; 26: 511-526.
  28. Tereshchenko J, Maddalena A, Bähr M, Kügler S. Pharmacologically controlled, discontinuous GDNF gene therapy restores motor function in a rat model of Parkinson’s disease. Neurobiology Diseases. 2014; 65: 35-42.
  29. Mesa-Infante V, Afonso-Oramas D, Salas-Hernández J, Rodríguez-Núñez J, Barroso-Chinea Long-term exposure to GDNF induces dephosphorylation of Ret, AKT, and ERK1/2, and is ineffective at protecting midbrain dopaminergic neurons in cellular models of Parkinson's disease. Molecular and Cellular Neuroscience. 2022; 118:103684.
  30. Conway JA, Kramer ER. Is activation of GDNF/RET signaling the answer for successful treatment of Parkinson's disease? A discussion of data from the culture dish to the clinic. Neural Regeneration Research. 2022; 17(7): 1462-1467.
  31. Abraham AG, O’Neill E. PI3K/Akt-mediated regulation of p53 in cancer Biochemical Society Transactions. 2014; 42(4): 798-803.
  32. Enterria-Morales D, Lopez-Lopez I, Lopez-Barneo J, d’Anglemont de Tassigny X. Role of glial cell line-derived neurotrophic factor in the maintenance of adult mesencephalic catecholaminergic neurons. Movement Disorders. 2020; 35: 565–576.
  33. Decressac M, Kadkhodaei B, Mattsson B, Laguna A, Perlmann T, et al. alpha-Synuclein-induced down-regulation of Nurr1 disrupts GDNF signaling in nigral dopamine neurons. Science Translational Medicine. 2012; 4(163):163ra156.
  34. Hulbert AJ, Pamplona R, Buffenstein R, Buttemer WA. Life and death: metabolic rate, membrane composition, and life span of animals. Physiological Reviews. 2007; 87: 1175–1213.
  35. Valvassori SS, Arent CO, Steckert AV, Varela RB, Jornada LK, Tonin PT, et al. Intracerebral Administration of BDNF Protects Rat Brain Against Oxidative Stress Induced by Ouabain in an Animal Model of Mania. Molecular Neurobiology. 2015; 52(1):353–62.
  36. Zigmond Triggering endogenous neuroprotective mechanisms in Parkinson’s disease: studies with a cellular model. Journal of Neural Transmission. 2006; 70: 439–442.
  37. Flensted-Jensen M, Gram M, Dela F, Helge JW, Larsen S. Six weeks of high intensity cycle training reduces H2O2 emission and increases antioxidant protein levels in obese adults with risk factors for type 2 diabetes. Free Radical Biology and Medicine. 2021; 173:1-6.
  38. Khani M, Zolfi H, Niknam Z. The effect of two-week high intensity interval training (HIIT) with Thyme supplementation on lipid profile, oxidative stress, body composition, and aerobic capacity of the obese and overweight women. Journal of Applied Health Studies in Sport Physiology. 2023; 10(2): 27-39.

 

  • Receive Date: 30 December 2023
  • Revise Date: 17 January 2024
  • Accept Date: 23 January 2024
  • First Publish Date: 23 January 2024
  • Publish Date: 21 January 2024