The effect of 8 week progressive resistant training on Agrin in Ft and St Muscles in aged male wistar Rats

Document Type : Research Paper

Authors

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Abstract

Back ground and purpose: Agrin is one the of important factor that contribute in maturation, stabilization and formation of neuromuscular junction (NMJ).usually cleavage of Agrin especially in aged people can cause NMJ destabilization and deterioration that result in sarcopenia in aged people. The purpose of the present study was to study of the effect of 8 week resistant training on agrin in Ft and St muscles in aged male wistar rat.
methodology: for this purpose 20 aged wistar rats (24 month), with weigh average of 485±3.5 after one week familiarization with laboratory condition randomly classified in two control (n=10) and training groups (n=10).training group protocol was ladder progressive training with carry of weights of 50%, 75%, 90% and 100% of the whole body weight of animals for 8 week and 3 section per week. Control group sustained in laboratory condition without any training. Forty-eight hours after the latest section of training period animals were anesthetized with ketamine and xaylazin. In surgical plane, the soleus and extensor digitrum lungous (EDL) muscles quickly removed and frozen with liquid nitrogen and then stored at -80оC until analysis. Western blot assay used for determining of protein changes in muscles tissue and independent T-test used for analyzes of data.
Results: analyze of data showed that the difference of soleus Agrin between control and training group was significant(p≤0.001).also results showed that EDL Agrin amount between training and control group was significantly different(p≤0.001).
Conclusion: since cleavage and decrease of Agrin can cause NMJ deterioration and result in sarcopenia, therefore with respect to this study finding, resistant training can have effective role to increase of Agrin and subsequently preventing of NMJ deterioration and sarcopenia in aged people.

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##Greenlund LJ,Nair KS.2003. Sarcopenia--consequences, mechanisms, and potential therapies. Mech Ageing Dev. 124: 287-99.##Lang T, et al.2010. Sarcopenia etiology, clinical consequences, intervention, and assessment. Osteoporos Int. 21: 543-59.##Lexell J, et al.1995. Heavy-resistance training in older Scandinavian men and women: short- and long-term effects on arm and leg muscles. Scand J Med Sci Sports. 5: 329-41.##Deschene MR.2004. Effects of aging on muscle fybre type and size .Sports Medicine.34:809–824.## Kung TA, Cederna PS, Meulen JH, Urbanchek MG, Faulkner JA.2013. Motor Unit Changes Seen With Skeletal Muscle Sarcopenia in Oldest Old Rats. J Gerontol A Biol Sci Med Sci.  42:563-579.##Dirks AJ, Leeuwenburgh C.2005.the role of apoptosis in age related skeletal muscle atrophy.Sports Medicine, vol. 35, no. 6, pp. 473–483.##Butikofer L,Zurlinden A, Bolliger MF, Kunz B, Sonderegger P.2011. Destabilizationof the neuromuscular junction by proteolytic cleavage of agrin results inprecocious sarcopenia. FASEB J. 25:4378–4393.##Bolliger MF, Zurlinden A, Luscher D, Butikofer L, Shakhova O, Francolini M,Kozlov SV, Cinelli P, Stephan A, Kistler AD, Rulicke T, Pelczar P,Ledermann B, Fumagalli G, Gloor SM, Kunz B, Sonderegger P.2010. Specificproteolytic cleavage of agrin regulates maturation of the neuromuscular junction.J. Cell Sci. 123:3944–3955.##Drey M,C.Sieber CC, Bauer JM, Uter W, Dahinden P, Fariello RG, Vrijbloed JV and the FiAT intervention group.2013. C-terminal Agrin Fragment as a potential marker for sarcopenia caused by degeneration of the neuromuscular junction. Experimental Gerontology 48 :76–80.##Tsen G, Halfter W, Kröger S, Cole GJ. 1995. Agrin is a heparan sulfate proteoglycan. J Biol Chem .270 : 3392–3399.## Gingras J, Rassadi S, Cooper E. Ferns M. 2002.Agrin plays an organizing role in the formation of sympathetic synapses. The Journal of cell biology. 158:1109-1118 .## Haitao Wu, Wen C, Xiong & Lin Mei.2010. To build a synapse: signaling pathways in neuromuscular junction assembly. Development.137: 1017-1033##Kroger S, Schröder JE .2002.Agrin in the developing CNS: new roles for a synapse organizer. News Physiol. Sci. 17 : 207–12.## Stefan Hettwer , Pius Dahinden , Stefan Kucsera , Carlo Farina ,Shaheen Ahmed , Ruggero Fariello , Michael Drey , Cornel Christian Sieber , Jan Willem Vrijbloed.2012. Elevated levels of a C-terminal agrin fragment identifies a new subset of sarcopenia patients. Experimental Gerontology.24:354-367.##Anne MS,  Micheal JW.1998.Agrin andacetylcholin receptor distribution fllowing electrical stimulation.Muscle & Nerve .407-409##Stefan Hettwer, Shuo Lin, Stefan Kucsera, Monika Haubitz, Filippo Oliveri, Ruggero G. Fariello,MA. Ruegg, Jan W, Vrijbloed.2014.Injection of a SolubleFragment of Neural Agrin (NT-1654) Considerably Improves the Muscle Pathology Caused by the Disassembly of the NeuromuscularJunction. PLOS ONE. 9:1-9.##Fragala MS, Jajtner AR, Beyer KS, Townsend JR, Emerson NS, Scanlon TC, Oliveira LP, Hoffman JR, Stout JR.2013. Biomarkers of muscle quality: N-terminal propeptide of type III procollagen and C-terminal agrin fragment responses to resistance exercise training in older adults. J Cachexia Sarcopenia Muscle. . 7:124-132.##Deschenes MR, Roby MA, Eason MK, Harris MB.2010.Remodeling of the neuromuscularjunction precedes sarcopenia related alterations in myofibers. Exp.Gerontol. 45:389–393.##Aagaard P, Suetta C, Caserotti P, Magnusson SP, Kjaer M.2010. Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure.Scand. J. Med. Sci. Sports 20:49–64.##Deschenes MR, Judelson DA, Kraemer WJ.2010.Effects of resistance training on neuromuscular junction morphology. Muscle Nerve .;23:1576–1581.##Spangenburg EE, Booth FW.2003. Molecular regulation of individual skeletal muscle fibre types. Acta Physiol Scand.178:413–424.##Matheny W,Merritt E,Zannikos SV,Farrar RP,Adamo ML.2009.Serum IGF-I deficiency does not prevent compensatory skeletal muscle hypertrophy in resistance exercise.Experimental Biology and Medicine.23:164-70.##