The effect of high-intensity interval swimming training on CREB and ERK proteins of hippocampus tissue in elderly rats

Document Type : Original Article

Authors

Department of Physical Education and Sport Science Yadegar-e-Imam Khomeini (RAH) Shahre-rey Branch, Islamic Azad University, Tehran, Iran

Abstract

Background and Purpose: Cognitive impairment caused by aging has become one of the most common health threats in many countries. Signaling pathways are important moderators of various physiological and pathological processes, and abnormal activation of some signaling pathways can play a role in disease progression in old age. Targets of intracellular signaling in response to exercise have been intensively studied as a measure of cellular processes that occur following specific conditions. It has been found that exercise increases neurogenesis through the induction of neural factors in the hippocampus, which is associated with improved cognitive performance, since long-term exercise can improve the age-related impairment in hippocampal neurogenesis. The aim of this study was to evaluate the effect of high-intensity interval swimming training on CREB and ERK proteins of hippocampus tissue in elderly rats.
Materials and Methods: In this experimental study, 12 aged male Sprague-Dawley rats (20 months old and average weight 300-450 gr) were placed in two control groups (n= 6 rats) and high-intensity interval swimming training (n= 6 rats). Rats in the training group performed high-intensity interval training (HIIT), including 14 times of 20 seconds of swimming with 10 seconds of rest between each time. The exercise program was carried out for six weeks (three days a week, one day in between). 48 hours after the last training session, rats were anesthetized and immediately, using a surgical blade, the skull was split and the brain was carefully removed. The healthy brain was divided into two halves by a surgical blade, and according to the coordinates of the hippocampus, the hippocampal sinus was separated from the limbic system with the help of a clean atlas. The content of cAMP-response element binding protein (CREB) and Extracellular signal-regulated protein kinases 1 and 2 (ERK) proteins in hippocampal tissue was measured by Western blotting. Data were analyzed using independent t-test at the P <0.05.
Results: The results showed that the protein content of ERK and CREB in the hippocampus of elderly rats after six weeks of training was significantly higher (P=0.03 and P=0.001, respectively) than untrained rats.
Conclusion: According to the results of high-intensity interval swimming training leads to a significant increase in the content of cAMP-response element binding protein and Extracellular signal-regulated protein kinases 1 and 2 of the hippocampus tissue in aged rats, so probably high-intensity interval swimming training can help improve factors involved in cognitive ability during aging.
 

Keywords

Main Subjects

References

  1. Raz N, Ghisletta P, Rodrigue KM, Kennedy KM. Lindenberger U. Trajectories of brain aging in middle-aged and older adults: regional and individual differences. Neuroimage 2010;51: 501–511
  2. Driscoll I, Howard SR, Stone JC, Monfils MH, Tomanek B, Brooks WM, Sutherland RJ. The aging hippocampus: a multi-level analysis in the rat. Neuroscience 2006;139: 1173–1185.
  3. Dickstein DL, Weaver CM, Luebke JI, Hof PR. Dendritic spine changes associated with normal aging. Neuroscience 2013;251:21-32.
  4. Yu XW, Curlik DM, Oh MM, Yin JC, Disterhoft JF. CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats. Elife. 2017;6:e19358.
  5. Viosca J, Malleret G, Bourtchouladze R, Benito E, Vronskava S, Kandel ER, et al. Chronic enhancement of CREB activity in the hippocampus interferes with the retrieval of spatial information. Learn Mem. 2009;16(3):198-209.
  6. Impey S, McCorkle SR, Cha-Molstad H, Dwyer JM, Yochum GS, Boss JM, et al. Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Cell. 2004;119:1041–1054.
  7. Steven A, Seliger B. Control of CREB expression in tumors: from molecular mechanisms and signal transduction pathways to therapeutic target. Oncotarget. 2016;7(23):35454-65.
  8. Kudo K, Wati H, Qiao C, Arita J, Kanba S. Age-related disturbance of memory and CREB phosphorylation in CA1 area of hippocampus of rats. Brain Research 2005;1054: 30–37
  9. Saura CA, Valero J. The role of CREB signaling in Alzheimer’s disease and other cognitive disorders. Journal of Neuroscience 2011;22:153–169
  10. Wang, H, Quirion R, Little PJ, Cheng Y, Feng ZP, Sun HS, et al. Forkhead box O transcription factors as possible mediators in the development of major depression. Neuropharmacology 2015;99;527–537.
  11. Altarejos JY, Montminy M. CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. nature reviews molecular cell biology 2011;12(3):141-51.
  12. Sakamoto K, Karelina K, Obrietan K. CREB: a multifaceted regulator of neuronal plasticity and protection. Journal of neurochemistry 2011;116:1–9.
  13. Satoh Y, Kobayashi Y, Takeuchi A, Pagès G, Pouysségur J, Kazama T. Deletion of ERK1 and ERK2 in the CNS causes cortical abnormalities and neonatal lethality: Erk1 deficiency enhances the impairment of neurogenesis in Erk2-deficient mice The Journal of neuroscience 2011;31:1149–1155
  14. Sun J, Nan G. The extracellular signal-regulated kinase 1/2 pathway in neurological diseases: A potential therapeutic target (Review). International journal of molecular medicine 2017;39(6):1338-1346.
  15. Song GY, Kang JS, Lee SY, Myung CS. Region-specific reduction of Gbeta4 expression and induction of the phosphorylation of PKB/Akt and ERK1/2 by aging in rat brain. Pharmacological research 2007;56:295–302
  16. Brown BM, Peiffer JJ, Martins RN. Multiple effects of physical activity on molecular and cognitive signs of brain aging: can exercise slow neurodegeneration and delay Alzheimer's disease? Molecular psychiatry 2013;18(8):864-74.
  17. Yang TT, Lo CP, Tsai PS, Wu SY, Wang TF, Chen YW, et al. Aging and exercise affect hippocampal neurogenesis via different mechanisms. PLoS One 2015;10: e0132152.
  18. Clark PJ, Bhattacharya TK, Miller DS, Rhodes JS. Induction of c-Fos, Zif268 and Arc from acute bouts of voluntary wheel running in new and pre-existing adult mouse hippocampal granule neurons. Neuroscience 2011;184: 16–27.
  19. Chen MJ, Russo-Neustadt AA. Running exercise-induced up-regulation of hippocampal brain-derived neurotrophic factor is CREB-dependent. Hippocampus 2009;19: 962–972.
  20. Williamson D, Gallagher P, Harber M, Hollon C, and Trappe S. Mitogen-activated protein kinase (MAPK) pathway activation: effects of age and acute exercise on human skeletal muscle. The Journal of physiology 2003;547:977–987.
  21. Brown BM, Peiffer JJ, Sohrabi HR, Mondal A, Gupta VB, Rainey-Smith S.R, et al. Intense physical activity is associated with cognitive performance in the elderly. Translational psychiatry 2012;2:e191.
  22. Jimenez-Maldonado A, Renteria I, Garcia-Suarez PC, Moncada-Jimenez J, Freire-Royes LF. The Impact of High-Intensity Interval Training on Brain Derived Neurotrophic Factor in Brain: A Mini-Review. Front Neurosci 2018;12:839
  23. Gurd BJ, Giles MD, Bonafiglia JT, Raleigh JP, Boyd JC, Ma JK, et al. Incidence of nonresponse and individual patterns of response following sprint interval training. Applied physiology, nutrition, and metabolism 2016;41:229–34.
  24. de Barbalho M, Gentil P, Izquierdo M, Fisher J, Steele J, Raiol R. There are no no-responders to low or high resistance training volumes among older women. Experimental gerontology 2017; 99:18–26.
  25. Pulimood NS, Rodrigues WDS Junior, Atkinson DA, Mooney SM, Medina AE. The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex. J Neurosci. 2017;37(28):6628-6637.
  26. Amirazodi F, Mehrabi A, Amirazodi M, Parsania S, Rajizadeh MA, Esmaeilpour K. The combination effects of resveratrol and swimming HIIT exercise on novel object recognition and open-field tasks in aged rats. Experimental aging research 2020;46(4):336-358.
  27. Braidy N, Poljak A, Grant R, Jayasena T, Mansour H, Chan-Ling T, et al. Differential expression of sirtuins in the aging rat brain. Frontiers in cellular neuroscience 2015;9:167.
  28. Lee SS, Kim CJ, Shin MS, Lim BV. Treadmill exercise ameliorates memory impairment through ERK-Akt-CREB-BDNF signaling pathway in cerebral ischemia gerbils. Journal of exercise rehabilitation 2020;16(1):49-57.
  29. ZHAO Y. Effects of exercise on ERK-CREB expression in rats with chronic stress. Chinese Journal of Public Health 2010;26(7): 848-849.
  30. Dalir T, Gharakhanlou R, Peeri M, Matin Homaee H. Effect of 8 weeks aerobic training on SRT1, CREB and BDNF genes expression in hippocampus of Wistar rats. The Journal of Sport and Biomotor Sciences 2018;11(19):11-18. (I n Persian)
  31. Fujioka T, Fujioka A, Duman RS. Activation of cAMP signaling facilitates the morphological maturation of newborn neurons in adult hippocampus. The Journal of neuroscience 2004;24:319–328.
  32. Zhu DY, Lau L, Liu SH, Wei JS, Lu YM. Activation of cAMP-response-element-binding protein (CREB) after focal cerebral ischemia stimulates neurogenesis in the adult dentate gyrus. Proceedings of the National Academy of Sciences 2004;101(25):9453-9457
  33. Rodríguez-Tornos FM, San Aniceto I, Cubelos B, Nieto M. Enrichment of Conserved Synaptic Activity-Responsive Element in Neuronal Genes Predicts a Coordinated Response of MEF2, CREB and SRF. PLoS ONE 2013;8(1):e53848.
  34. Mekari S, Neyedli HF, Fraser S, O’Brien MW, Martins R, Evans K, et al. High-Intensity Interval Training Improves Cognitive Flexibility in Older Adults. Brain Sciences 2020; 10(11):796
  35. Whitfield TW, Jr, Shi X, Sun WL, McGinty JF. The suppressive effect of an intra-prefrontal cortical infusion of BDNF on cocaine seeking is Trk receptor and extracellular signal-regulated protein kinase mitogen-activated protein kinase dependent. The Journal of neuroscience. 2011;31:834–842.
  36. Lonze BE, Ginty DD. Function and regulation of CREB family transcription factors in the nervous system. Neuron 2002;35:605–623.
  37. Baghaiee B, Karimi P, Siahkouhian M, Pescatello L. Moderate aerobic exercise training decreases middle-aged induced pathologic cardiac hypertrophy by improving Klotho expression, MAPK signaling pathway and oxidative stress status in Wistar rats. Iranian Journal of Basic Medical Sciences 2018;21(9): 911-919.
  38. Jamshidi M, Kordi M, Shabkhiz F. Effect of involuntary and voluntary exercise in an enrichment environment on astrogliosis reaction of hippocampus white matter in type 3 diabetic rat models. Journal of Sport and Exercise Physiology 2022; 54-66. (I n Persian)
  39. Rezaei AR, Gaeini, AA, Choobineh S, Nuri R. The effect of six weeks High Intensity Interval Swimming Training and Resveratrol supplementation on the level of SIRT3 in left ventricular heart of aged rats". Journal of Sport and Exercise Physiology 2022; 15(3): 25-34. (I n Persian)
  40. Constans A, Pin-Barre C, Molinari F, Temprado JJ, Brioche T, Pellegrino C, et al. High-intensity interval training is superior to moderate intensity training on aerobic capacity in rats: Impact on hippocampal plasticity markers. Behav Brain Res. 2021; 398:112977.

Files

History

  • Receive Date: 08 October 2022
  • Revise Date: 18 January 2023
  • Accept Date: 29 January 2024
  • First Publish Date: 29 January 2024
  • Publish Date: 22 June 2023

Share

How to cite

Statistics