Improving soleus muscle function in male Wistar rats by increasing calcitonin gene-dependent peptide (CGRP) during a period of moderate-intensity continuous rehabilitation training

Document Type : Research Paper

Authors

1 Department of Physical Education, Boroujerd Branch, Islamic Azad University, Boroujerd, Iran

2 Department of Physical Education, Razi University, Kermanshah, Iran

Abstract

Background and aim: Decreased physical activity is associated with poor neuromuscular function for daily activities. Laboratory studies indicate the effect of calcitonin gene-related peptide (CGRP) on neuromuscular activity. The aim of this study was to investigate the effect of a course of moderate-intensity continuous rehabilitation exercises (MCT) on CGRP expression in skeletal muscle of male Wistar rats.
Materials and Methods: For this purpose, 12 male Wistar rats weighing 200-220 g, with a sleep cycle of 12.12, free access to food and water and ambient temperature of 25±2 ° C were randomly divided into two groups of exercise and control. The training group performed 6 sessions (5 sessions per week) of continuous training with moderate intensity. The conditions of the control group were similar to the training group but they did not exercise. Finally, 48 hours after the last training session, rats were extracted by standard anesthesia, victim and horseshoe muscle method of all mice, and then Western blot method was used to determine the expression of CGRP protein. Significance level was considered p> 0.05.
Results: Statistical findings from the output of independent t-test for CGRP receptor protein expression values showed that the implementation of six weeks of MCT training protocol significantly increased CGRP protein expression in the MCT group compared with the control group (P = 0.048).
Conclusion: These results indicate that the MCT rehabilitation protocol caused that muscle function during endurance activities could be improved by increasing CGRP protein expression.

Keywords


Amara, S. G., Jonas, V., Rosenfeld, M. G., Ong, E. S., & Evans, R. M. (1982). “Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products”. Nature, 298(5871), 240-244. doi:10.1038/298240a0
Ashina, H., Iljazi, A., Al-Khazali, H. M., Christensen, C. E., Amin, F. M., Ashina, M., & Schytz, H. W. (2020). “Hypersensitivity to Calcitonin GeneRelated Peptide in Post-Traumatic Headache”. Ann Neurol, 88(6), 1220-1228. doi:10.1002/ana.25915
Aveseh, M., Koushki Jahromi, M., Nemati, J., & Esmaieli Mahani, S. (2019). “Acute and Chronic Effects of Endurance Training on CGRP Gene Expression in the Brain, CSF, and Serum of Male Wistar Rats”. Sport Physiology, 11(41), 137-152 doi:10.22089/spj.2017.4486.1602. (In Persian)
Carmine Belin, A., Ran, C., & Edvinsson, L. (2020). “Calcitonin Gene-Related Peptide (CGRP) and Cluster Headache”. Brain sciences, 10(1), 30. doi:10.3390/brainsci10010030
Chae, C. H., Jung, S. L., An, S. H., Jung, C. K., Nam, S. N., & Kim, H. T. (2011). “Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating pphosphatidylinositol 3-kinase activation in the soleus of diabetic rats”. J Physiol Biochem, 67(2), 235-241. doi: 10.1007/s13105-010-0068-9
Cottrell, G. S. (2019). “CGRP Receptor Signalling Pathways”. Handb Exp Pharmacol, 255, 37-64. doi:10.1007/164_2018_130
Darabaneanu, S., Overath, C., Rubin, D., Lüthje, S., Sye, W., Niederberger, U., ... Weisser, B. (2011). “Aerobic Exercise as a Therapy Option for Migraine: A Pilot Study”. Int J Sports Med, 32, 455- 460. doi:10.1055/s-0030-1269928
Deschenes, M. R., Tufts, H. L., Oh, J., Li, S., Noronha, A. L., & Adan, M. A. (2020). “Effects of exercise training on neuromuscular junctions and their active zones in young and aged muscles”. Neurobiol Aging, 95, 1-8. doi: 10.1016/j.neurobiolaging.2020.07.001
Eftekhari, S., Salvatore, C. A., Johansson, S., Chen, T. B., Zeng, Z., & Edvinsson, L. (2015). “Localization of CGRP, CGRP receptor, PACAP and glutamate in trigeminal ganglion. Relation to the blood-brain barrier”. Brain Res, 1600, 93-109. doi:10.1016/j.brainres.2014.11.031
Emson, P. C., & Zaidi, M. (1989). “Further evidence for the origin of circulating calcitonin gene-related peptide in the rat”. The Journal of physiology, 412, 297-308. doi:10.1113/jphysiol.1989.sp017616
Forsgren, S., Bergh, A., Carlsson, E., & Thornell, L. E. (1993). “Calcitonin gene-related peptide expression at endplates of different fibre types in muscles in rat hind limbs”. Cell Tissue Res, 274(3), 439-446. doi:10.1007/bf00314540
Gharakhanlou, R., Parnow, A., Hedayati, M., Mahdian, R., & Rajabi, S. (2009). “Effects of Endurance and Resistance training on Calcitonin Gene-Related Peptide Content in Slow and Fast Twitch Rat Muscles”. Iranian Journal of Endocrinology & Metabolism, 11, 307-313. (In Persian)
Gorzi, A., Jazaei, R., Rahmani, A., & Bahari, A. (2020). “The effects of different rest interval durations between resistance exercise sets on gene expression of CGRP and IGF-1 of muscle in male wistar rats”. Research in Sport Medicine Technology, 9(18 #g001105). (In Persian)
Homonko, D. A., & Theriault, E. (1997). “Calcitonin gene-related peptide is increased in hindlimb motoneurons after exercise”. Int J Sports Med, 18(7), 503-509. doi:10.1055/s-2007-972672
Homonko, D. A., & Theriault, E. (2000). “Downhill running preferentially increases CGRP in fast glycolytic muscle fibers”. J Appl Physiol (1985), 89(5), 1928-1936. doi:10.1152/jappl.2000.89.5.1928
Jonhagen, S., Ackermann, P., Saartok, T., & Renstrom, P. A. (2006). “Calcitonin gene related peptide and neuropeptide Y in skeletal muscle after eccentric exercise: a microdialysis study”. Br J Sports Med, 40(3), 264-267; discussion 264-267. doi: 10.1136/bjsm.2005.022731
Khorshidvand, M., Gharakhanlou, R., & Hassan Sajedi, R. (2019). “The Effect of Moderate Continuous Training on TRPV1 Protein Expression in Slow-Contraction Muscles of Wistar Rats”. SPORT BIOSCIENCES (HARAKAT), 11(1 #b00971). (In Persian)
Iyengar, S., Johnson, K. W., Ossipov, M. H., & Aurora, S. K. (2019). “CGRP and the Trigeminal System in Migraine”. Headache, 59(5), 659-681. doi:10.1111/head.13529
Iyengar, S., Ossipov, M. H., & Johnson, K. W. (2017). “The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine”. Pain, 158(4), 543-559. doi: 10.1097/j.pain.0000000000000831
Leira, Y., Ameijeira, P., Domínguez, C., López-Arias, E., Ávila-Gómez, P., Pérez-Mato, M., ... Blanco, J. (2020). “Severe periodontitis is linked with increased peripheral levels of sTWEAK and PTX3 in chronic migraineurs”. Clin Oral Investig, 24(2), 597-606. doi:10.1007/s00784-019-02950-9
Parnow, A., Eslami, R., & Gharakhanlou, R. (2012). “Effects of Physical Activity on Calcitonin GeneRelated Peptide Content at Trigeminal Ganglion Nerve in Wistar Rats”. J Mazand Univ Med Sci, 22, 25-31. (In Persian)
Parnow, A., Gharakhanlou, R., Gorginkaraji, Z., Rajabi, S., Eslami, R., Hedayati, M., & Mahdian, R. (2012). “Effects of endurance and resistance training on calcitonin gene-related Peptide and acetylcholine receptor at slow and fast twitch skeletal muscles and sciatic nerve in male Wistar rats”. Int J Pept, 2012, 962651. (In Persian) doi:10.1155/2012/962651
Recober, A., Kuburas, A., Zhang, Z., Wemmie, J. A., Anderson, M. G., & Russo, A. F. (2009). “Role of calcitonin gene-related peptide in light-aversive behavior: implications for migraine”. J Neurosci, 29(27), 8798-8804. doi:10.1523/jneurosci.1727- 09.2009
Sakaguchi, M., Inaishi, Y., Kashihara, Y., & Kuno, M. (1991). “Release of calcitonin gene-related peptide from nerve terminals in rat skeletal muscle”. The Journal of physiology, 434, 257-270. doi:10.1113/jphysiol.1991.sp018468
Umoh, N. A., Walker, R. K., Millis, R. M., AlRubaiee, M., Gangula, P. R., & Haddad, G. E. (2014). “Calcitonin Gene-Related Peptide Regulates Cardiomyocyte Survival through Regulation of Oxidative Stress by PI3K/Akt and MAPK Signaling Pathways”. Ann Clin Exp Hypertens, 2(1), 1007.
Varkey, E., Cider, A., Carlsson, J., & Linde, M. (2011). “Exercise as migraine prophylaxis: a randomized study using relaxation and topiramate as controls”. Cephalalgia, 31(14), 1428-1438. doi:10.1177/0333102411419681
Vega, A., & Avila, G. (2010). “CGRP, a Vasodilator Neuropeptide that Stimulates Neuromuscular Transmission and EC Coupling”. Current vascular pharmacology, 8, 394-403. doi:10.2174/157016110791112287
Viru, A. (2017). Adaptation in Sports Training. London Routledge.
Wang, X., & Fiscus, R. R. (1997). “Lactic acid potentiates bradykinin- and low-pH-induced release of CGRP from rat spinal cord slices”. Am J Physiol, 273 (1 Pt 1), E92-98. doi:10.1152/ajpendo.1997.273.1.E92
Wattiez, A. S., Sowers, L. P., & Russo, A. F. (2020). “Calcitonin gene-related peptide (CGRP): role in migraine pathophysiology and therapeutic targeting”. Expert Opin Ther Targets, 24(2), 91-100. doi:10.1080/14728222.2020.1724285
Zhu, J., Pedersen, M. D., Ahmed, L. S., Abdolalizadeh, B., Grell, A. S., Berg, J. O., . . . Hansen, P. R. (2020). “Fluorescent Analogues of Human α- Calcitonin Gene-Related Peptide with Potent Vasodilator Activity”. Int J Mol Sci, 21(4). doi:10.3390/ijms21041343
­