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Effects of Physical Training in Different Modes on Cognitive Function and GNDF Level in Old Mice

We compared the effects of physical high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the cognitive functions in old mice and on serum levels of glial cell line-derived neurotrophic factor (GDNF) in these animals. Thirty old (aged 22 months) mice were divided into control (no training), MICT, and HIIT groups; the training protocol (treadmill running) was applied for 8 weeks. The spontaneous alternation test (Y-maze) and inhibitory avoidance test were used to assess cognitive function. The GDNF levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique. Both HIIT and MICT cycles improved cognitive functions compared to those in the control group; HIIT provided a greater improvement than MICT, and this difference was significant in the inhibitory avoidance test. Both training cycles increased the serum GDNF level compared with the control group; however, this increase was greater in the HIIT group. Thus, both HIIT and MICT could improve cognitive functions in old mice and increase the serum GNDF level, but HIIT seems to provide greater beneficial effects by resulting in a greater increase in the amount of this neurotrophic factor.

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References

  1. A. M. Fjell, M. H. Sneve, H. Grydeland, et al., “The disconnected brain and executive function decline in aging,” Cereb. Cortex, 27, No. 3, 2303–2317 (2017), https://doi.org/10.1093/cercor/bhw082.

    Article  PubMed  Google Scholar 

  2. A. Miyake, N. P. Friedman, M. J. Emerson, et al., “The unity and diversity of executive functions and their contributions to complex “Frontal Lobe” tasks: a latent variable analysis,” Cogn. Psychol., 41, No. 1, 49–100 (2000), https://doi.org/10.1006/cogp.1999.0734.

    CAS  Article  PubMed  Google Scholar 

  3. L. R. Clark, D. M. Schiehser, G. H. Weissberger, et al., “Specific measures of executive function predict cognitive decline in older adults,” J. Int. Neuropsychol. Soc., 18, No. 1, 118–127 (2012), https://doi.org/10.1017/S1355617711001524.

    Article  PubMed  Google Scholar 

  4. G. C. Rowe, A. Safdar, and Z. Arany, “Running forward: new frontiers in endurance exercise biology,” Circulation, 129, No. 7, 798–810 (2014), https://doi.org/10.1161/CIRCULATIONAHA.113.001590.

    Article  PubMed  PubMed Central  Google Scholar 

  5. M. W. Voss, C. Vivar, A. F. Kramer, and H. van Praag, “Bridging animal and human models of exercise-induced brain plasticity,” Trends Cogn. Sci., 17, No. 10, 525–544 (2013), https://doi.org/10.1016/j.tics.2013.08.001.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Y. M. Heo, M. S. Shin, J. M. Lee, et al., “Treadmill exercise ameliorates short-term memory disturbance in scopolamine-induced amnesia rats,” Int. Neurourol. J., 18, No. 1, 16–22 (2014), https://doi.org/10.5213/inj.2014.18.1.16.

    Article  PubMed  PubMed Central  Google Scholar 

  7. J. M. Lee, M. S. Shin, E. S. Ji, et al., “Treadmill exercise improves motor coordination through ameliorating Purkinje cell loss in amyloid beta23-35-induced Alzheimer’s disease rats,” J. Exerc. Rehabil., 10, No. 5, 258–264 (2014), https://doi.org/10.12965/jer.140163.

    Article  PubMed  PubMed Central  Google Scholar 

  8. J. M. Lee, T. W. Kim, S. S. Park, et al., “Treadmill exercise improves motor function by suppressing Purkinje cell loss in Parkinson disease rats,” Int. Neurourol. J., 22, Suppl. 3, S147–S1155 (2018), https://doi.org/10.5213/inj.1836226.113.

    Article  PubMed  PubMed Central  Google Scholar 

  9. C. E. Garber, B. Blissmer, M. R. Deschenes, et al., “Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise,”. Med. Sci. Sports Exerc. 43, No. 7, 1334–1359 (2011), https://doi.org/10.1249/MSS.0b013e318213fefb.

    Article  PubMed  Google Scholar 

  10. G. Fisher, A. W. Brown, M. M. Bohan Brown, et al. “High intensity interval- vs. moderate intensity-training for improving cardiometabolic health in overweight or obese males: a randomized controlled trial”. PLoS One., 10, e0138853 (2015).

  11. R. Daabis, M. Hassan, and M. Zidan, “Endurance and strength training in pulmonary rehabilitation for COPD patients,” Egpt. J. Chest Dis. Tuberc., 66, 231–236 (2017), https://doi.org/10.1016/j.ejcdt.2016.07.003.

    Article  Google Scholar 

  12. K. S. Weston, U. Wisløff, and J. S. Coombes, “High-intensity interval training in patients with lifestyle-induced cardiometabolic disease: a systematic review and meta-analysis,” Br. J. Sports Med., 48, No. 16, 1227–1234 (2014), https://doi.org/10.1136/bjsports-2013-092576.

    Article  PubMed  Google Scholar 

  13. M. J. Gibala, J. P. Little, M. van Essen, et al., “Short-term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance,” J. Physiol., 575, Pt. 3, 901–911 (2006), https://doi.org/10.1113/jphysiol.2006.112094.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. A. Jiménez-Maldonado, I. Rentería, P. C. García-Suárez, et al., “The impact of high-intensity interval training on brain derived neurotrophic factor in brain: a minireview,” Front. Neurosci., 12, 839 (2018), https://doi.org/10.3389/fnins.2018.00839.

    Article  PubMed  PubMed Central  Google Scholar 

  15. C. L. C. Campêlo, J. R. Santos, A. F. Silva, et al., “Exposure to an enriched environment facilitates motor recovery and prevents short-term memory impairment and reduction of striatal BDNF in a progressive pharmacological model of parkinsonism in mice,” Behav. Brain Res., 328, 138–148 (2017), https://doi.org/10.1016/j.bbr.2017.04.028.

    CAS  Article  PubMed  Google Scholar 

  16. R. T. de Oliveira, L. A. Felippe, L. T. Bucken, et al., “Benefits of exercise on the executive functions in people with Parkinson disease: a controlled clinical trial,” Am. J. Phys. Med. Rehabil., 96, No. 5, 3010–306 (2017), https://doi.org/10.1097/PHM.0000000000000612.

    Article  Google Scholar 

  17. Y. K. Jeon and C. H. Ha, “The effect of exercise intensity on brain derived neurotrophic factor and memory in adolescents,” Environ. Health Prev. Med., 22, No. 1, 27 (2017), https://doi.org/10.1186/s12199-017-0643-6.

  18. A. Kovacevic, B. Fenesi, F. Paolucci, and J. J. Heisz, “The effects of aerobic exercise intensity on memory in older adults,” Appl. Physiol. Nutr. Metab., 45, No. 6, 591–600 (2020), https://doi.org/10.1139/apnm-2019-0495.

    Article  PubMed  Google Scholar 

  19. D. Moreau, I. J. Kirk, and K. E. Waldie, “High-intensity training enhances executive function in children in a randomized, placebo-controlled trial,” Elife, 6, e25062 (2017), doi: https://doi.org/10.7554/eLife.25062.

  20. H. Pallesen, M. Bjerk, A. R. Pedersen, et al., “The effects of high-intensity aerobic exercise on cognitive performance after stroke: a pilot randomised controlled trial,” J. Cent. Nerv. Syst. Dis., 11, 1179573519843493 (2019), https://doi.org/10.1177/1179573519843493.

    Article  PubMed  PubMed Central  Google Scholar 

  21. S. Mekari, H. F. Neyedli, S. Fraser, et al., “High-intensity interval training improves cognitive flexibility in older adults,” Brain Sci., 10, No, 11, 796 (2020), https://doi.org/10.3390/brainsci10110796.

  22. M. Pertusa, S. García-Matas, H. Mammeri H, et al., “Expression of GDNF transgene in astrocytes improves cognitive deficits in aged rats,” Neurobiol. Aging., 29, No. 9, 1366–1379 (2008), https://doi.org/10.1016/j.neurobiolaging.2007.02.026.

  23. O. V. Forlenza, A. S. Miranda, I. Guimar, et al., “Decreased neurotrophic support is associated with cognitive decline in non-demented subjects,” J. Alzheimers Dis., 46, No. 2, 423–429 (2015), https://doi.org/10.3233/JAD-150172.

    CAS  Article  PubMed  Google Scholar 

  24. R. Gerlai, A. McNamara, D. L. Choi-Lundberg, et al., “Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutation,” Eur. J. Neurosci., 14, No. 7, 1153–1163 (2001), https://doi.org/10.1046/j.0953-816x.2001.01724.x.

    CAS  Article  PubMed  Google Scholar 

  25. S. F. Martinez-Huenchullan, B. R. Maharjan, P. F. Williams, et al., “Differential metabolic effects of constant moderate versus high intensity interval training in high-fat fed mice: possible role of muscle adiponectin,” Physiol. Rep., 6, No. 4, e13599 (2018), https://doi.org/10.14814/phy2.13599.

  26. A. Sabaghi, A. Heirani, H. Mahmoodi, and S. Sabaghi,”” High-intensity interval training prevents cognitive-motor impairment and serum BDNF level reduction in Parkinson mice model,” Sport Sci. Health, 15, No. 13, 681–687 (2019), https://doi.org/10.1007/s11332-019-00586-6.

  27. A. Sabaghi, A. Heirani, N. Yousofvand, et al., “Comparison of high-intensity interval training and moderate-intensity continuous training in their effects on behavioral functions and CORT levels in streptozotocin-induced diabetic mice,” Sport Sci. Health, 17, No. 9785, 119–126 (2021), https://doi.org/10.1007/s11332-020-00661-3.

    Article  Google Scholar 

  28. WHO, “Aging and Health,” Available online: https://www.who.int/news-room/fact-sheets/detail/ageing-and-health (accessed on 1 November 2019)

  29. UN, “Ageing,” Available online: https://www.un.org/en/sections/issues-depth/ageing/ (accessed on 18 May 2020).

  30. C. Benedict, S. J. Brooks, J. Kullberg, et al., “Association between physical activity and brain health in older adults,” Neurobiol. Aging, 34, No. 1, 83–90 (2013), https://doi.org/10.1016/j.neurobiolaging.2012.04.013.

    Article  PubMed  Google Scholar 

  31. L. Donath, S. Ludyga, D. Hammes, et al., “Absolute and relative reliability of acute effects of aerobic exercise on executive function in seniors,” BMC Geriatr., 17, No. 1, 247 (2017).

  32. F. Gheysen, L. Poppe, A. DeSmet, et al., “Physical activity to improve cognition in older adults: can physical activity programs enriched with cognitive challenges enhance the effects? A systematic review and meta-analysis,” Int. J. Behav. Nutr. Phys. Act., 15, No. 1, 63 (2018), https://doi.org/10.1186/s12966-018-0697-x.

  33. E. Santana-Sosa, M. I. Barriopedro, L. M. López-Mojares, et al., “Exercise training is beneficial for Alzheimer’s patients,” Int. J. Sports Med., 29, No. 10, 845–850 (2008), https://doi.org/10.1055/s-2008-1038432.

    CAS  Article  PubMed  Google Scholar 

  34. E. B. Larson, L. Wang, J. D. Bowen, et al., “Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older,” Ann. Intern. Med., 144. No. 2, 73–81 (2006), https://doi.org/10.7326/0003-4819-144-2-200601170-00004.

    Article  PubMed  Google Scholar 

  35. N. T. Lautenschlager, K. L. Cox, L. Flicker, et al., “Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial,” JAMA, 300, No.9, 1027–1037 (2008), https://doi.org/10.1001/jama.300.9.1027.

  36. Z. Radak, N. Hart, L. Sarga, et al., “Exercise plays a preventive role against Alzheimer’s disease,” J. Alzheimers Dis., 20, No. 3, 777–783 (2010), https://doi.org/10.3233/JAD-2010-091531.

    Article  PubMed  Google Scholar 

  37. K. I. Erickson, A. G. Gildengers, and M. A. Butters, “Physical activity and brain plasticity in late adulthood,” Dialogues Clin. Neurosci., 15. No.1, 99–108 (2013), https://doi.org/10.31887/DCNS.2013.15.1/kerickson.

  38. L. Chaddock-Heyman, K. I. Erickson, J. L. Holtrop, et al., “Aerobic fitness is associated with greater white matter integrity in children,” Front. Hum. Neurosci., 8, 584 (2014), https://doi.org/10.3389/fnhum.2014.00584.

    Article  PubMed  PubMed Central  Google Scholar 

  39. L. Mandolesi, F. Gelfo, L. Serra L, et al., “Environmental factors promoting neural plasticity: insights from animal and human studies,” Neural Plast., 2017, 7219461 (2017), https://doi.org/10.1155/2017/7219461.

  40. K. I. Erickson, R. S. Prakash, M. W. Voss, et al., “Aerobic fitness is associated with hippocampal volume in elderly humans,” Hippocampus, 19, No. 10, 1030–1039 (2009), https://doi.org/10.1002/hipo.20547.

    Article  PubMed  PubMed Central  Google Scholar 

  41. A. L. Groover, J. M. Ryals, B. L. Guilford, et al., “Exercise-mediated improvements in painful neuropathy associated with prediabetes in mice,” Pain, 154, No. 12, 2658–2667 (2013), https://doi.org/10.1016/j.pain.2013.07.052.

    Article  PubMed  Google Scholar 

  42. M. E. Afzalpour, H. T. Chadorneshin, M. Foadoddini, and H. A. Eivari, “Comparing interval and continuous exercise training regimens on neurotrophic factors in rat brain,” Physiol. Behav., 147, 78–83 (2015), https://doi.org/10.1016/j.physbeh.2015.04.012.

    CAS  Article  PubMed  Google Scholar 

  43. S. Siamilis, J. Jakus, C. Nyakas C, et al., “The effect of exercise and oxidant-antioxidant intervention on the levels of neurotrophins and free radicals in spinal cord of rats,” Spinal Cord, 47, No. 6, 453–457 (2009), https://doi.org/10.1038/sc.2008.125.

  44. M. Guo, V. Lin, W. Davis, et al., “Preischemic induction of TNF-alpha by physical exercise reduces blood-brain barrier dysfunction in stroke,” J. Cereb. Blood Flow Metab., 28, No. 8, 1422–1430 (2008), https://doi.org/10.1038/jcbfm.2008.29.

    CAS  Article  PubMed  Google Scholar 

  45. Y. H. Ding, C. N. Young, X. Luan, et al., “Exercise preconditioning ameliorates inflammatory injury in ischemic rats during reperfusion,” Acta. Neuropathol., 109, No. 3, 237–246 (2005), https://doi.org/10.1007/s00401-004-0943-y.

    CAS  Article  PubMed  Google Scholar 

  46. S. Li, Y. Wang, Z. Wang, et al., “Enhanced renoprotective effect of GDNF-modified adipose-derived mesenchymal stem cells on renal interstitial fibrosis,” Stem Cell. Res. Ther., 12, No. 1, 27 (2021), https://doi.org/10.1186/s13287-020-02049-z.

  47. S. Sun, F. Li, X. Gao X, et al., “Calbindin-D28K inhibits apoptosis in dopaminergic neurons by activation of the PI3-kinase-Akt signaling pathway,” Neuroscience, 119, 359–367 (2011),

  48. S. Sun, Q. Zhang, M. Li, et al., “GDNF promotes survival and therapeutic efficacy of human adipose-derived mesenchymal stem cells in a mouse model of Parkinson’s disease,” Cell. Transplant., 29, 963689720908512 (2020), https://doi.org/10.1177/0963689720908512.

  49. M. Duarte Azevedo, S. Sander, and L. Tenenbaum, “GDNF, a neuron-derived factor upregulated in glial cells during disease,” J. Clin. Med., 9, No. 2, 456 (2020), https://doi.org/10.3390/jcm9020456.

  50. K. Yamagata, M. Tagami, K. Ikeda, et al., “Differential regulation of glial cell line-derived neurotrophic factor (GDNF) mRNA expression during hypoxia and reoxygenation in astrocytes isolated from stroke-prone spontaneously hypertensive rats,” Glia, 37, No. 1, 1–7 (2002), https://doi.org/10.1002/glia.10003.

    Article  PubMed  Google Scholar 

  51. A. Saavedra, G. Baltazar, and E. P. Duarte, “Driving GDNF expression: the green and the red traffic lights,” Prog. Neurobiol., 86, No. 3, 186–215 (2008), https://doi.org/10.1016/j.pneurobio.2008.09.006.

    CAS  Article  PubMed  Google Scholar 

  52. J. J. Heisz, M. G. Tejada, E. M. Paolucci, and C. Muir, “Enjoyment for high-intensity interval exercise increases during the first six weeks of training: implications for promoting exercise adherence in sedentary adults,” PLoS One, 11, No. 12, e0168534 (2016), https://doi.org/10.1371/journal.pone.0168534.

  53. C. M. Saucedo Marquez, B. Vanaudenaerde, T. Troosters, and N. Wenderoth, “High-intensity interval training evokes larger serum BDNF levels compared with intense continuous exercise,” J. Appl. Physiol. (1985), 119, No. 12, 1363–1373 (2015), https://doi.org/10.1152/japplphysiol.00126.2015.

  54. J. J. Chapman, J. S. Coombes, W. J. Brown, et al., “The feasibility and acceptability of high-intensity interval training for adults with mental illness: A pilot study,” Mental Health Phys. Act., 13, 40–48 (2017), https://doi.org/10.1016/j.mhpa.2017.09.007.

    Article  Google Scholar 

  55. M. A. Wewege, D. Ahn, J. Yu, et al., “High-intensity interval training for patients with cardiovascular disease – is it safe? A systematic review,” J. Am. Heart Assoc., 7, No. 21, e009305 (2018), https://doi.org/10.1161/JAHA.118.009305.

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Sarvat, S., Sabaghi, A., Yosofvand, N. et al. Effects of Physical Training in Different Modes on Cognitive Function and GNDF Level in Old Mice. Neurophysiology 53, 132–139 (2022). https://doi.org/10.1007/s11062-022-09924-w

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  • DOI: https://doi.org/10.1007/s11062-022-09924-w

Keywords

  • old mice
  • physical high-intensity interval training (HIIT)
  • moderate-intensity continuous training (MICT)
  • cognitive function
  • alteration and avoidance tests
  • GDNF