Journal of Sport and Exercise Physiology

Journal of Sport and Exercise Physiology

The effect of two types of moderate and high intensity aerobic exercise on the levels of monocarboxylate transporters type 2 and 4 in the cortex and striatum of healthy and stroke Wistar rats models

Document Type : Original Article

Authors
Mosayeb Rastegar Harooki 1
Rasoul Rezaei 2
Javad Nemati 1
Mohsen Salesi 1
Mohammad Hemmatinafar 1
1 Department of Sports Science, Faculty of Educational Sciences and Psychology, Shiraz University. Shiraz. Iran
2 department of sport sciences, faculty of educational sciences and psychology Shiraz university, Shiraz, Iran
10.48308/joeppa.2024.235855.1261
Abstract
Background and Purpose: Monocarboxylate transporters type 2 and 4 (MCT2 and MCT4) levels are high in brain tissue, which can be useful in postponing fatigue during exercise by transporting lactate in the brain.
Therefore, the purpose of this research was to investigate the effects of two types of aerobic exercise with different intensities on the amounts of MCT2 and MCT4 in the cortex and striatum of healthy and stroke Wistar rats models.
Materials and Methods: In the present research 60 male Wistar rats (8 weeks old) were randomly divided into ten groups of control and healthy moderate intensity continuous training (MICT) and high intensity interval training (HIIT) of  24 and 72-hour stroke (6 rats in each group). The MICT and HIIT protocol consisted of three parts: warm-up, main exercise and cool-down. The training period lasted for 4 weeks, 5 sessions per week and each session lasted 32 minutes. The MICT protocol was performed at an intensity corresponding to 70% of the maximum speed and the HIIT protocol at an intensity of 85-90% of the maximum speed. Stroke was induced by blocking the carotid artery. The content of MCT2 and MCT4 was measured by Western blot technique in the cortex and striatum of the brain. Data analysis were performed by using one-way ANOVA and Tukey's post hoc tests in SPSS software version 29 and GraphPad Prism version 2.2.10 at a significance level of p≤0.05.
Results: Significant differences in the content of cortical tissue MCT2 (p=0.59)  and the content of striatum tissue MCT2 (p=0.66) and MCT4 (p=0.22) were not found after four weeks of MICT and HIIT in healthy and stroke groups. However, MCT4 content in cortical tissue showed a significant difference after 72 hours of stroke (p<0.05). Tukey's post-hoc test for MCT4 content showed a significant difference between the 72-hour stroke HIIT groups compared to the 72-hour stroke MICT (p=0.02), 72-hour stroke control (p=0.04), 24-hour stroke HIIT (p=0.01), 24-hour stroke MICT (p=0.009), 24-hour stroke control (p=0.003), and MICT (p=0.02) groups.
Conclusion: It seems that MICT and HIIT do not have a significant effect on the content of MCT2 and MCT4 in the brain. However, in the cortical tissue, a significant difference was observed in the MCT4 of the HIIT group with a 72-hour stroke compared to the other groups, and this could indicate the withdrawal of lactate by the MCT4 72 hours after the stroke and recovery.
Keywords
Exercise Training
Stroke
Monocarboxylate Type 2
Monocarboxylate Type 4
Subjects
  1. Adoukonou T, Agbétou M, Bangbotche R, Kossi O, Mefo PF, Magne J, et al. Long-term mortality of stroke survivors in Parakou: 5-year follow-up. Journal of Stroke and Cerebrovascular Diseases. 2020;29(6):104785.
  2. Yamagata K. Lactate Supply from Astrocytes to Neurons and its Role in Ischemic Stroke-induced Neurodegeneration. Neuroscience. 2022;481:219-31.
  3. Yu X, Zhang R, Wei C, Gao Y, Yu Y, Wang L, et al. MCT2 overexpression promotes recovery of cognitive function by increasing mitochondrial biogenesis in a rat model of stroke. Animal Cells and Systems. 2021;25(2):93-101.
  4. Lushchak VI, Duszenko M, Gospodaryov DV, Garaschuk O. Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point. Antioxidants (Basel). 2021;10(11).
  5. Zhu XH, Lu M, Chen W. Quantitative imaging of brain energy metabolisms and neuroenergetics using in vivo X-nuclear (2)H, (17)O and (31)P MRS at ultra-high field. J Magn Reson. 2018;292:155-70.
  6. Monsorno K, Ginggen K, Ivanov A, Buckinx A, Lalive AL, Tchenio A, et al. Loss of microglial MCT4 leads to defective synaptic pruning and anxiety-like behavior in mice. Nature Communications. 2023;14(1):5749.
  7. Li R, Yang Y, Wang H, Zhang T, Duan F, Wu K, et al. Lactate and Lactylation in the Brain: Current Progress and Perspectives. Cellular and Molecular Neurobiology. 2023;43(6):2541-55.
  8. Plourde G, Roumes H, Suissa L, Hirt L, Doche É, Pellerin L, et al. Neuroprotective effects of lactate and ketone bodies in acute brain injury. Journal of Cerebral Blood Flow & Metabolism.0(0):0271678X241245486.
  9. Karagiannis A, Gallopin T, Lacroix A, Plaisier F, Piquet J, Geoffroy H, et al. Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity. Elife. 2021;10:e71424.
  10. Pérez-Escuredo J, Van Hée VF, Sboarina M, Falces J, Payen VL, Pellerin L, Sonveaux P. Monocarboxylate transporters in the brain and in cancer. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2016;1863(10):2481-97.
  11. Ueno M, Chiba Y, Murakami R, Miyai Y, Matsumoto K, Wakamatsu K, et al. Distribution of Monocarboxylate Transporters in Brain and Choroid Plexus Epithelium. Pharmaceutics. 2023;15(8):2062.
  12. EL-Seedy A, Pellerin L, Page G, Ladeveze V. Identification of Intron Retention in the Slc16a3 Gene Transcript Encoding the Transporter MCT4 in the Brain of Aged and Alzheimer-Disease Model (APPswePS1dE9) Mice. Genes. 2023;14(10):1949.
  13. Sun X, Wang M, Wang M, Yao L, Li X, Dong H, et al. Role of Proton-Coupled Monocarboxylate Transporters in Cancer: From Metabolic Crosstalk to Therapeutic Potential. Frontiers in Cell and Developmental Biology. 2020;8.
  14. Lundquist AJ, Llewellyn GN, Kishi SH, Jakowec NA, Cannon PM, Petzinger GM, Jakowec MW. Knockdown of Astrocytic Monocarboxylate Transporter 4 in the Motor Cortex Leads to Loss of Dendritic Spines and a Deficit in Motor Learning. Molecular Neurobiology. 2022;59(2):1002-17.
  15. Pang R, Wang X, Du Z, Pei F, Li Z, Sun L, et al. The distribution and density of monocarboxylate transporter 2 in cerebral cortex, hippocampus and cerebellum of wild-type mice. Journal of Anatomy. 2020;236(2):370-7.
  16. Medel V, Crossley N, Gajardo I, Muller E, Barros LF, Shine JM, Sierralta J. Whole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function. Proceedings of the National Academy of Sciences. 2022;119(33):e2204619119.
  17. Han P, Zhang W, Kang L, Ma Y, Fu L, Jia L, et al. Clinical Evidence of Exercise Benefits for Stroke. Adv Exp Med Biol. 2017;1000:131-51.
  18. Rosenfeldt AB, Linder SM, Davidson S, Clark C, Zimmerman NM, Lee JJ, Alberts JL. Combined Aerobic Exercise and Task Practice Improve Health-Related Quality of Life Poststroke: A Preliminary Analysis. Arch Phys Med Rehabil. 2019;100(5):923-30.
  19. Freitas DA, Rocha-Vieira E, De Sousa RAL, Soares BA, Rocha-Gomes A, Chaves Garcia BC, et al. High-intensity interval training improves cerebellar antioxidant capacity without affecting cognitive functions in rats. Behavioural Brain Research. 2019;376:112181.
  20. Freitas DA, Rocha-Vieira E, Soares BA, Nonato LF, Fonseca SR, Martins JB, et al. High intensity interval training modulates hippocampal oxidative stress, BDNF and inflammatory mediators in rats. Physiology & Behavior. 2018;184:6-11.
  21. Takimoto M, Hamada T. Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins. Journal of Applied Physiology. 2014;116(9):1238-50.
  22. Béland-Millar A, Takimoto M, Hamada T, Messier C. Brain and muscle adaptation to high-fat diets and exercise: Metabolic transporters, enzymes and substrates in the rat cortex and muscle. Brain Research. 2020;1749:147126.
  23. Park J, Kim J, Mikami T. Exercise-Induced Lactate Release Mediates Mitochondrial Biogenesis in the Hippocampus of Mice via Monocarboxylate Transporters. Frontiers in Physiology. 2021;12.
  24. Bedford TG, Tipton CM, Wilson NC, Oppliger RA, Gisolfi CV. Maximum oxygen consumption of rats and its changes with various experimental procedures. Journal of Applied Physiology. 1979;47(6):1278-83.
  25. Leandro CG, Levada AC, Hirabara SM, MANHAS-DE-CASTRO R, De-Castro CB, Curi R, Pithon-Curi TC. Aprogram of moderate physical training for wistar rats based on maximal oxygen consumption. The Journal of Strength & Conditioning Research. 2007;21(3):751-6.
  26. Ramez M, Rajabi H, Ramezani F, Naderi N, Darbandi-Azar A, Nasirinezhad F. The greater effect of high-intensity interval training versus moderate-intensity continuous training on cardioprotection against ischemia-reperfusion injury through Klotho levels and attenuate of myocardial TRPC6 expression. BMC cardiovascular disorders. 2019;19:1-10.
  27. Rezaei R, Nasoohi S, Haghparast A, Khodagholi F, Bigdeli MR, Nourshahi M. High intensity exercise preconditioning provides differential protection against brain injury following experimental stroke. Life Sciences. 2018;207:30-5.
  28. Rousselet E, Kriz J, Seidah NG. Mouse model of intraluminal MCAO: cerebral infarct evaluation by cresyl violet staining. JoVE (Journal of Visualized Experiments). 2012(69):e4038.
  29. Magistretti PJ, Allaman I. Lactate in the brain: from metabolic end-product to signalling molecule. Nature reviews neuroscience. 2018;19(4):235-49.
  30. Falkowska A, Gutowska I, Goschorska M, Nowacki P, Chlubek D, Baranowska-Bosiacka I. Energy metabolism of the brain, including the cooperation between astrocytes and neurons, especially in the context of glycogen metabolism. International journal of molecular sciences. 2015;16(11):25959-81.
  31. Bhatti MS, Frostig RD. Astrocyte-neuron lactate shuttle plays a pivotal role in sensory-based neuroprotection in a rat model of permanent middle cerebral artery occlusion. Scientific Reports. 2023;13(1):12799.
  32. Benítez‐Muñoz JA, Cupeiro R, Rubio‐Arias JÁ, Amigo T, González‐Lamuño D. Exercise influence on monocarboxylate transporter 1 (MCT1) and 4 (MCT4) in the skeletal muscle: A systematic review. Acta Physiologica. 2024:e14083.
  33. Gao C, Yang B, Li Y, Pei W. Monocarboxylate transporter-dependent mechanism is involved in the adaptability of the body to exercise-induced fatigue under high-altitude hypoxia environment. Brain Research Bulletin. 2023;195:78-85.
  34. Zhang W. Regular Exercise Affects the Expression of Monocarboxylate Transporters in Brains of AD Model Mice and Improves Cognitive Function. Acta Microscopica. 2019;28(2).
  35. Lev-Vachnish Y, Cadury S, Rotter-Maskowitz A, Feldman N, Roichman A, Illouz T, et al. L-lactate promotes adult hippocampal neurogenesis, Front. Neurosci. 13 (2019) 403. 2019.
  36. Winstein CJ, Stein J, Arena R, Bates B, Cherney LR, Cramer SC, et al. Guidelines for adult stroke rehabilitation and recovery: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(6):e98-e169.
  37. Lee S, Choi Y, Jeong E, Park J, Kim J, Tanaka M, Choi J. Physiological significance of elevated levels of lactate by exercise training in the brain and body. Journal of Bioscience and Bioengineering. 2023;135(3):167-75.
  38. Chen G, Wan W, Yurong L, Wenjuan P. Expression and Significance of Monocarboxylate Transporters in Cortex of Rats After Exercise-induced Fatigue. Laboratory Animal and Comparative Medicine. 2022;42(1):42.
  39. Matsui T, Omuro H, Liu Y-F, Soya M, Shima T, McEwen BS, Soya H. Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity. Proceedings of the National Academy of Sciences. 2017;114(24):6358-63.
  40. Seyedi R, Tayebi SM, Zhang D, Yiming Q. The role of monocarboxylate transporter-1 and -4 in exercise and training: A mini-review article. Science & Sports. 2024;39(2):144-52.
  41. Horii N, Hasegawa N, Fujie S, Uchida M, Miyamoto-Mikami E, Hashimoto T, et al. High-intensity intermittent exercise training with chlorella intake accelerates exercise performance and muscle glycolytic and oxidative capacity in rats. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2017;312(4):R520-R8.
  42. Thomas C, Bishop DJ, Lambert K, Mercier J, Brooks GA. Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2012.
  43. Chatel B, Bendahan D, Hourdé C, Pellerin L, Lengacher S, Magistretti P, et al. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice. The FASEB Journal. 2017;31(6):2562-75.
  44. Scariot PPM, Manchado-Gobatto FB, Beck WR, Papoti M, Van Ginkel PR, Gobatto CA. Monocarboxylate transporters (MCTs) in skeletal muscle and hypothalamus of less or more physically active mice exposed to aerobic training. Life Sciences. 2022;307:120872.
  45. Han P, Zhang W, Kang L, Ma Y, Fu L, Jia L, et al. Clinical Evidence of Exercise Benefits for Stroke. In: Xiao J, editor. Exercise for Cardiovascular Disease Prevention and Treatment: From Molecular to Clinical, Part 2. Singapore: Springer Singapore; 2017. p. 131-51.
  46. Lu Y, Li M, Zhuang Y, Lin Z, Nie B, Lei J, et al. Combination of fMRI and PET reveals the beneficial effect of three-phase enriched environment on post-stroke memory deficits by enhancing plasticity of brain connectivity between hippocampus and peri-hippocampal cortex. CNS Neuroscience & Therapeutics. 2024;30(3):e14466.
  47. Xue X, Liu B, Hu J, Bian X, Lou S. The potential mechanisms of lactate in mediating exercise-enhanced cognitive function: a dual role as an energy supply substrate and a signaling molecule. Nutrition & Metabolism. 2022;19(1):52.
  48. Elizondo-Vega R, García-Robles MA. Molecular characteristics, regulation, and function of monocarboxylate transporters. Glial Amino Acid Transporters. 2017:255-67.

 

 

  • Receive Date 12 June 2024
  • Revise Date 05 July 2024
  • Accept Date 09 July 2024
  • First Publish Date 09 July 2024
  • Publish Date 21 June 2024