Document Type : Research Paper

Authors

1 Ph.D. Student of Sport Physiology, Shiraz University

2 Associate Professor of Sport Physiology, Shiraz University

3 Assistance Professor of Sport Physiology ؟, Shiraz University

4 Associate Professor of Biology, Shahid Bahonar University of Kerman

Abstract

The study aimed to investigate the acute and chronic effects of endurance training on calcitonin gene-related peptide (CGRP) in the brain, cerebrospinal fluid (CSF), and serum in male Wistar rats. Frothy animals were equally divided into four groups including control, acute, trained chronic, and trained acute. The acute group performed only one endurance exercise session, trained acute performed a single exercise session following a twelve-week endurance training, and trained chronic performed twelve-week of endurance training. CSF was collected from the cisterna magena and various parts of the brain were extracted. CSF and serum concentration of CGRP and its gene expression were measured by ELISA and Real Time-PCR technique, respectively. Statistical test of One-way ANOVA was used for data analysis. Compared with control group, CGRP concentration in CSF (acute: P=0.006; trained acute: P=0.008) and serum (acute: P=0.009; trained acute: P=0.007) increased significantly. CGRP gene expression increased only in the cortex of the acute (P = 0.007) and trained acute (P = 0.006) in comparison to control group; Compared with the acute group, CGRP gene expression increased in the cortex of the trained acute group (P = 0.018). The chronic effect of exercise did not appear in any of research variables in trained chronic group. In conclusion, CGRP increment in CSF and serum during endurance exercise is likely due to its enhanced expression in the cortex. In addition, resting values of CSF and serum CGRP are not affected by long-term endurance exercise; however, they are subjected to exercise response to adaptation. 

Keywords

Main Subjects

  1. Poyner DR, Sexton PM, Marshall I, Smith DM, Quirion R, Born W, et al. International union of pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev. 2002;54(2):233-46.
  2. Skofitsch G, Jacobowitz DM. Quantitative distribution of calcitonin gene-related peptide in the rat central nervous system. Peptides. 1985;6(6):1069-73.
  3. Russell FA, King R, Smillie SJ, Kodji X, Brain SD. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014;94(4):1099-142.
  4. Brain SD, Grant AD. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev. 2004;84(3):903-34.
  5. Zhang ZH, Fang XB, Xi GM, Li WC, Ling HY, Qu P. Calcitonin gene-related peptide enhances CREB phosphorylation and attenuates tau protein phosphorylation in rat brain during focal cerebral ischemia/reperfusion. Biomed Pharmacother. 2010;64(6):430-6.
  6. Liu Z, Liu Q, Cai H, Xu C, Liu G, Li Z. Calcitonin gene-related peptide prevents blood-brain barrier injury and brain edema induced by focal cerebral ischemia reperfusion. Regul Pept. 2011;171(1-3):19-25.
  7. Yang SI, Yuan Y, Jiao S, Luo QI, Yu J. Calcitonin gene-related peptide protects rats from cerebral ischemia/reperfusion injury via a mechanism of action in the MAPK pathway. Biomed Rep. 2016;4(6):699-703.
  8. Iyengar S, Ossipov MH, Johnson KW. The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine. Pain. 2017;158(4):      543-59.
  9. Leighton B, Cooper GJ. Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro. Nature. 1988;335(6191):632-5.
  10. Leighton B, Foot EA. The role of the sensory peptide calcitonin-gene-related peptide(s) in skeletal muscle carbohydrate metabolism: effects of capsaicin and resiniferatoxin. Biochem J. 1995;307:707-12.
  11. Rossetti L, Farrace S, Choi SB, Giaccari A, Sloan L, Frontoni S, et al. Multiple metabolic effects of CGRP in conscious rats: role of glycogen synthase and phosphorylase. Am J Physiol. 1993;264(1 Pt 1):1-10.
  12. Hasbak P, Lundby C, Olsen NV, Schifter S, Kanstrup IL. Calcitonin gene-related peptide and adrenomedullin release in humans: Effects of exercise and hypoxia. Regul Pept. 2002;108(2-3):89-95.
  13. Sun XJ, Pan SS. Role of calcitonin gene-related peptide in cardioprotection of short-term and long-term exercise preconditioning. J Cardiovasc Pharmacol. 2014;64(1):53-9.
  14. Parnow A, Gharakhanlou R, Gorginkaraji Z, Rajabi S, Eslami R, Hedayati M, et al. Effects of endurance and resistance training on calcitonin gene-related peptide and acetylcholine receptor at slow and fast twitch skeletal muscle and sciatic nerve in male Wistar rats. Int J Pept. 2012;2012:1-8.
  15. Homonko DA, Theriault E. Downhill running preferentially increases CGRP in fast glycolytic muscle fibers. J Appl Physiol. 2000;89(5):1928-36.
  16. Kregel KC, Allen DL, Booth FW, Fleshner MR, Henriksen EJ, Musch TI, et al. Resource book for the design of animal exercise protocols. California:American Physiological Society; 2006. p. 85.
  17. Pegg CC, He C, Stroink AR, Kattner KA, Wang CX. Technique for collection of cerebrospinal fluid from the cisterna magna in rat. J Neurosci Methods. 2010;187(1):8-12.
  18. Enoki T, Yoshida Y, Lally J, Hatta H, Bonen A. Testosterone increases lactate transport, monocarboxylate transporter (MCT) 1 and MCT4 in rat skeletal muscle. J Physiol. 2006;577(Pt 1):433-43.
  19. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8.
  20. 20-Thomas AG, Dennis A, Bandettini PA, Johansen-Berg H. The effects of aerobic activity on brain structure. Front Psychol. 2012;3:86. doi: 10.3389/fpsyg.2012.00086.
  21. Hoffmann J, Wecker S, Neeb L, Dirnagl U, Reuter U. Primary trigeminal afferents are the main source for stimulus-induced CGRP release into jugular vein blood and CSF. Cephalalgia. 2012;32(9):659-67.
  22. Barker RA, Cicchetti F. Neuroanatomy and Neuroscience at a Glance. 4th ed. Cambridge: John Wiley & Sons; 2012. p. 90.
  23. Zechner R, Zimmermann R, Eichmann TO, Kohlwein SD, Haemmerle G, Lass A, et al. Fat signals-lipases and lipolysis in lipid metabolism and signaling. Cell Metab. 2012;15(3):279-91. 
  24. Emson PC, Zaidi M. Further evidence for the origin of circulating calcitonin gene-related peptide in the rat. J Physiol. 1989;412:297-308.
  25. Sakaguchi M, Inaishi Y, Kashihara Y, Kuno M. Release of calcitonin gene-related peptide from nerve terminals in rat skeletal muscle. J Physiol. 1991;434:257-70.
  26. Yamada M, Ishikawa T, Yamanaka A, Fujimori A, Goto K. Local neurogenic regulation of rat hindlimb circulation: CO2-induced release of calcitonin gene-related peptide from sensory nerves. Br J Pharmacol. 1997;122:710-4.
  27. Wang X, Fiscus RR. Lactic acid potentiates bradykinin-and low-pH-induced release of CGRP from rat spinal cord slices. Am J Physiol. 1997;273:92-8.