Daneshvar Medicine

Daneshvar Medicine

The effect of HIIT and CGRP inhibition on EGF and EGFR gene expression in the hippocampal tissue of male Wistar rats

Document Type : Original Article

Authors
Asma Jafari Khooshan Abadi 1
Sajjad Ramezani 2
Shila Nayebifar 1
1 Faculty of Psychology and Educational Sciences, Department of Sports Sciences, University of Sistan and Baluchistan, Zahedan, Iran
2 Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran
10.22070/daneshmed.2023.17102.1298
Abstract
Background and Objective: Growth factors are small peptide biomolecules that play an important role in increasing autoimmune diseases and are involved in the pathogenesis of many types of cancer. The main purpose of this study is to investigate the effect of 6 weeks of HIIT with inhibition of CGRP on EGF and EGFR gene expression in the hippocampal tissue of male Wistar rats.
Materials and Methods: In this experimental study, 32 Wistar male laboratory rats with an average weight of 205±15 grams and an age of 8 weeks were randomly divided into 4 groups of 8 series including         1-control (C), 2-inhibition of CGRP (CI), 3-HIIT (TH). ) and               4-inhibition of CGRP+HIIT (CI+TH) were divided. In order to inhibit CGRP in groups 2 and 4, CGRP antibody was used intraperitoneally at a dose of 0.25 mg/kg. The HIIT training protocol was performed for 6 weeks and 5 days per week, which consisted of 10 bouts of intense       2-minute running. on the treadmill and 1 minute of slow running (active rest) was incremental. Finally, the desired tissue was extracted and the expression level of EGF and EGFR genes was evaluated by Real time-PCRΔΔ method and using 2 ΔΔCt formula. To analyze the findings, one-way analysis of variance was used along with Tukey's post hoc test in SPSS software version 26 (p≤0.05).
Results: The results of the present study showed that the levels of EGF in hippocampal tissue in group (TH) were significantly higher than groups (CI) (P=0.001) and (C) (P=0.006). It was also significantly higher in the (CI+TH) group than the (CI) group (P=0.007). EGFR gene expression levels in   (CI+TH) group were significantly higher than (CI) (P=0.04) and (TH) (P=0.01).
Conclusion: Physiological changes caused by HIIT in the hippocampus can improve the functional state of the brain through positive regulation of EGF and EGFR gene expression as an effective non-pharmacological method. Furthermore, HIIT+CGRP inhibition may represent a novel approach through the EGF and EGFR pathways in the hippocampus.
Keywords
High-Intensity Interval Trainings (HIIT)
Epidermal Growth Factor (EGF)
Calcitonin Gene-Related Peptide (CGRP)
Hippocampus
  1. Pouranvari S, Ebrahimi F, Javadi G, Maddah B. Production of recombinant human epidermal growth factor and assessment of its activity in cell viability. Journal of Mazandaran University of Medical Sciences 2015;25(125):10-20.
  2. Wang Q, Xu L, Wu Q, Zhang M, Zhang J. Association between the risk of hepatitis virus-related hepatocellular carcinoma and EGF polymorphism: A PRISMA-compliant updated meta-analysis. Medicine 2022;101(42):e31280.
  3. Sirigireddy V. A comparative study of effect of epidermal growth factor on chronic leg ulcers with anti-septic dressing. International Surgery Journal 2021;8(10):2910-5.
  4. Meybosch S, De Monie A, Anné C, Bruyndonckx L, Jürgens A, De Winter BY, et al. Epidermal growth factor and its influencing variables in healthy children and adults. PloS One 2019;14(1):e0211212.
  5. Marinović S, Berković MC, Zjačić-Rotkvić V, Kapitanović S. Analysis of polymorphisms in EGF, EGFR and HER2 genes in pancreatic neuroendocrine tumors (PNETs). Cancer Genetics 2022;266:44-50.
  6. Rajaram P, Chandra P, Ticku S, Pallavi B, Rudresh K, Mansabdar P. Epidermal growth factor receptor: Role in human cancer. Indian Journal of Dental Research 2017;28(6):687.
  7. Shoorgashti R, Sadri D, Farhadi S. Expression of Epidermal Growth Factor Receptor by Odontogenic Cysts: A comparative Study of Dentigerous Cyst and Odontogenic Keratocyst. ournal of Research in Dental Sciences 2020;17(2):127-36.
  8. Edvinsson L, Warfvinge K. The CGRP Family of Neuropeptides and their Receptors in the Trigeminovascular System. Monoclonal Antibodies in Headache: Springer 2021;1-12.
  9. Russell FA, King R, Smillie S-J, Kodji X, Brain S. Calcitonin gene-related peptide: physiology and pathophysiology. Physiological Reviews 2014;94(4):1099-142.
  10. Aveseh M, Koushki Jahromi M, Nemati J, Esmaieli Mahani S. Acute and Chronic Effects of Endurance Training on CGRP Gene Expression in The Brain, CSF, And Serum of Male Wistar Rats. Sport Physiology 2019;11(41):137-52.
  11. Rossetti L, Farrace S, Choi S, Giaccari A, Sloan L, Frontoni S, et al. Multiple metabolic effects of CGRP in conscious rats: role of glycogen synthase and phosphorylase. American Journal of Physiology-Endocrinology and Metabolism 1993;264(1):E1-E10.
  12. Hashikawa-Hobara N, Ogawa T, Sakamoto Y, Matsuo Y, Ogawa M, Zamami Y, et al. Calcitonin gene-related peptide pre-administration acts as a novel antidepressant in stressed mice. Scientific Reports 2015;5(1):1-14.
  13. Singh Y, Gupta G, Shrivastava B, Dahiya R, Tiwari J, Ashwathanarayana M, et al. Calcitonin gene‐related peptide (CGRP): A novel target for Alzheimer's disease. CNS Neuroscience & Therapeutics 2017;23(6):457-61.
  14. Russo AF. Calcitonin gene-related peptide (CGRP): a new target for migraine. Annual Review of Pharmacology and Toxicology 2015;55:533.
  15. Borkum JM. CGRP and brain functioning: cautions for migraine treatment. Headache:The Journal of Head and Face Pain 2019;59(8):1339-57.
  16. Holzer P, Pabst M, Lippe IT, Peskar B, Peskar B, Livingston E, et al. Afferent nerve-mediated protection against deep mucosal damage in the rat stomach. Gastroenterology 1990;98(4):838-48.
  17. Zhai L, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Tanaka M, et al. Endogenous calcitonin gene-related peptide suppresses ischemic brain injuries and progression of cognitive decline. Journal of Hypertension 2018;36(4):876-91.
  18. Melo CS, Rocha-Vieira E, Freitas DA, Soares BA, Rocha-Gomes A, Riul TR, et al. A single session of high-intensity interval exercise increases antioxidants defenses in the hippocampus of Wistar rats. Physiology & Behavior 2019;211:112675.
  19. Naghibzadeh M, Ranjbar R, TABANDEH M, Habibi A. Effect of High Intensity Exercise Preconditioning on the Prevention of Myelin damage in Hippocampus of Male C57BL/6 Mice. SJIMU 2019;27(1):122-136.
  20. Rogoz K, Andersen HH, Kullander K, Lagerström MC. Glutamate, substance P, and calcitonin gene-related peptide cooperate in inflammation-induced heat hyperalgesia. Molecular Pharmacology 2014;85(2):322-34.
  21. Sun P, Wei S, Wei X, Wang J, Zhang Y, Qiao M, et al. Anger emotional stress influences VEGF/VEGFR2 and its induced PI3K/AKT/mTOR signaling pathway. Neural Plasticity 2016;2016(10).41:1-12.
  22. Verboven M, Cuypers A, Deluyker D, Lambrichts I, Eijnde BO, Hansen D, et al. High intensity training improves cardiac function in healthy rats. Scientific Reports 2019;9(1):1-8.
  23. Yasar Z, Elliott BT, Kyriakidou Y, Nwokoma CT, Postlethwaite RD, Gaffney CJ, et al. Sprint interval training (SIT) reduces serum epidermal growth factor (EGF), but not other inflammatory cytokines in trained older men. European Journal of Applied Physiology 2021;121(7):1909-19.
  24. Choi SY, Lee YJ, Kim JM, Kang HJ, Cho SH, Chang SE. Epidermal growth factor relieves inflammatory signals in staphylococcus aureus-treated human epidermal keratinocytes and atopic dermatitis-like skin lesions in Nc/Nga mice. BioMed Research International 2018 15;2018:9439182. doi: 10.1155/2018/9439182. eCollection 2018..
  25. Rayego-Mateos S, Rodrigues-Diez R, Morgado-Pascual JL, Valentijn F, Valdivielso JM, Goldschmeding R, et al. Role of epidermal growth factor receptor (EGFR) and its ligands in kidney inflammation and damage. Mediators of Inflammation 2018;2018(10).87:1-22.
  26. Accattato F, Greco M, Pullano SA, Carè I, Fiorillo AS, Pujia A, et al. Effects of acute physical exercise on oxidative stress and inflammatory status in young, sedentary obese subjects. PloS one 2017;12(6):e0178900.
  27. Diaz-Castro J, Moreno-Fernandez J, Chirosa I, Chirosa LJ, Guisado R, Ochoa JJ. Beneficial effect of ubiquinol on hematological and inflammatory signaling during exercise. Nutrients 2020;12(2):424.
  28. Ciano M, Mantellato G, Connolly M, Paul-Clark M, Willis-Owen S, Moffatt MF, et al. EGF receptor (EGFR) inhibition promotes a slow-twitch oxidative, over a fast-twitch, muscle phenotype. Scientific Reports 2019;9(1):1-9.
  29. Zare M, Nayebifar S, Aminizadeh S, Vahidian-Rezazadeh M. The Effects of Six Weeks of Endurance Training and CGRP Inhibition on Nrf2 and AKT Expression in the Hippocampal Tissue of Male Wistar Rats. Mediators of Inflammation. 2022;2022(10).16:1-9.
  30. Barari AR, Hadian S, Amini S. Effect of Aloe Vera and Swimming Training on Serum Levels of Epidermal Growth Receptors (HER2, EGFR), in mice with Breast Cancer. Iranian Quarterly Journal of Breast Disease 2017;10(3):31-40.
  31. Cheng G, Mei Y, Pan X, Liu M, Wu S. Expression of HER2/c-erbB-2, EGFR protein in gastric carcinoma and its clinical significance. Open Life Sciences 2018;14(1):119-25.
  32. Song M, Lee KM, Kang D. Breast cancer prevention based on gene–environment interaction. Molecular Carcinogenesis 2011;50(4):280-90.
  33. Haug T, Storm JF. Protein kinase A mediates the modulation of the slow Ca2+-dependent K+ current, I sAHP, by the neuropeptides CRF, VIP, and CGRP in hippocampal pyramidal neurons. Journal of Neurophysiology 2000;83(4):2071-9.
  34. Luo H-m, Wu X, Liu W-x, Wang L-y, Sun H-y, Zhu L-y, et al. Calcitonin gene-related peptide attenuates angiotensin II-induced ROS-dependent apoptosis in vascular smooth muscle cells by inhibiting the CaMKII/CREB signalling pathway. Biochemical and Biophysical Research Communications 2020;521(2):285-9.
  35. Shamsi B, Abedi B, Ramezani S. The effect of eight weeks of resistance training with consumption of Tribulus terrestris extract on antioxidant indices of hippocampal tissue in male rats exposed to stanazol. Journal of Applied Health Studies in Sport Physiology 2022;9(1):48-60.
  36. Arjmand A, Abedi B, Hosseini SA, Ramezani S. The Effect of Resistance Training with Tribulus terrestris Extract on Apoptosis of Heart Tissue in Rats. Journal of North Khorasan University of Medical Sciences 2021;13(2):70-6.
Daneshvar Medicine
Volume 30, Issue 6 - Serial Number 163
January and February 2023
Pages 10-19