Document Type : Research Paper
Authors
Abstract
The structure and function of neuromuscular junction (NMJ) changes significantly during aging and results in decrease of physical performance and sarcopenia. The purpose of this study was to determine the effect of eight weeks of endurance training and neuronal nitric oxide synthase (nNOS( inhibition on skeletal muscle nicotinic acetylcholine receptors (nAchR) in old rats. Endogenous NO production was blocked by two administering NG-nitro-L- arginine methyl ester (L-NAME) dosages (25 and 100 mg-1.kg-1.day-1) solved in drinking water. Forty eight old male Wistar rats (20 months) were randomly divided into six groups: control, LNAME25, LNAME100, endurance training with LNAME25, endurance training with LNAME100 and training. LNAME treatment began 48 hrs before exercise protocol and continued until the last day. Endurance training groups were exercised on treadmill for 8 weeks, 5 times a week and 60 minutes a day at velocity up to 28 m/min. Forty eight hours after last session of exercise training, animals were anesthetized and soleus and Extensor digitorum longus (EDL) were removed. Western Blotting analysis revealed that training increased nAchR level (P0.05) and nNOS inhibition decreased it (P0.05) compared to the control group. Our data showed that training groups which received LNAME (25 and 100 mg-1/kg-1/day-1), nAchR level increased significantly (P0.05) compare to control group. Our data suggested that daily endurance training could increase nAchR level even in rats which received LNAME and NO signaling has a role in regulation of nAchR level. In general, daily training could be a suitable route to reduce sarcopenia in aged population.
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1) Gallegly Jc, Turesky NA, Strotman BA, Gurley CM, Peterson CA, Dupont-Versteegden EE. Satellite cell regulation of muscle mass is altered at old age. Journal of Applied Physiology. 2004;97(3):1082-90.
2) Marcell TJ. Sarcopenia: causes, consequences, and preventions. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2003;58(10):911-6.
3) Narici MV, Maffulli N. Sarcopenia: characteristics, mechanisms and functional significance. British medical bulletin. 2010;95(1):139-59.
4) Frontera WR, Hughes VA, Fielding RA, Fiatarone MA, Evans WJ, Roubenoff R. Aging of skeletal muscle: a 12-yr longitudinal study. Journal of Applied Physiology. 2000; 88(4):1321-6.
5) Hughes VA, Frontera WR, Wood M, Evans WJ, Dallal GE, Roubenoff R, et al. Longitudinal Muscle Strength Changes in Older Adults Influence of Muscle Mass, Physical Activity, and Health. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2001; 56(5):209-17.
6) Kadi F, Charifi N, Denis C, Lexell J. Satellite cells and myonuclei in young and elderly women and men. Muscle & nerve. 2003; 29(1):120-7.
7) Lukaszyk A, Bodzenta-Lukaszyk A, Aksiucik A, Gabryelewicz A, Konturek S, Bielawiec M. The role of epidermal growth factor in platelet-endothelium interactions. Journal of physiology and pharmacology. 1998; 49:229-40.
8) Chien MY, Kuo HK, Wu YT. Sarcopenia, cardiopulmonary fitness, and physical disability in community-dwelling elderly people. Physical therapy. 2010; 90(9):1277-87.
9) Fry CS, Glynn EL, Drummond MJ, Timmerman KL, Fujita S, Abe T, et al. Blood flow restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in older men. Journal of Applied Physiology. 2010; 108(5):1199-209.
10) Doherty TJ. Invited review: aging and sarcopenia. Journal of Applied Physiology. 2003; 95(4):1717-27.
11) Edström E, Altun M, Bergman E, Johnson H, Kullberg S, Ramírez-León V, et al. Factors contributing to neuromuscular impairment and sarcopenia during aging. Physiology & behavior. 2007; 92(1):129-35.
12) Jang YC, Van Remmen H. Age-associated alterations of the neuromuscular junction. Experimental gerontology. 2011; 46(2):193-8.
13) Punga AR, Ruegg MA. Signaling and aging at the neuromuscular synapse: lessons learnt from neuromuscular diseases. Current Opinion in Pharmacology. 2012; 12(3): 340-6.
14) Hoch W. Formation of the neuromuscular junction. European Journal of Biochemistry. 2001; 265(1):1-10.
15) Kalamida D, Poulas K, Avramopoulou V, Fostieri E, Lagoumintzis G, Lazaridis K, et al. Muscle and neuronal nicotinic acetylcholine receptors. FEBS Journal. 2007; 274(15):3799-845.
16) Desaulniers P, Lavoie P-A, Gardiner PF. Endurance training increases acetylcholine receptor quantity at neuromuscular junctions of adult rat skeletal muscle. Neuroreport. 1998; 9(16):3549-52.
17) Fahim MA. Endurance exercise modulates neuromuscular junction of C57BL/6NNia aging mice. Journal of Applied Physiology. 1997; 83(1):59-66.
18) Deschenes MR, Judelson DA, Kraemer WJ, Meskaitis VJ, Volek JS, Nindl BC, et al. Effects of resistance training on neuromuscular junction morphology. Muscle & nerve. 2000; 23(10):1576-81.
19) Gorgin Karaji Z, Parnoo A, Gharakhanlou R, Rajabi S. The Effect of Endurance Training on amount of Nicotinic Acetylcholine Receptors (nAChR) in Fast and Slow Twitch Muscle of Male Wistar Rats. Journal of Kermanshah University of Medical Sciences. 2013; 16(7):518-24.
20) Huh KH, Fuhrer C. Clustering of nicotinic acetylcholine receptors: from the neuromuscular junction to interneuronal synapses. Molecular neurobiology. 2002; 25(1):79-112.
21) Godfrey EW, Schwarte RC. The role of nitric oxide signaling in the formation of the neuromuscular junction. Journal of neurocytology. 2003; 32(5):591-602.
22) Moncada S, Higgs E. Molecular mechanisms and therapeutic strategies related to nitric oxide. The FASEB journal. 1995; 9(13):1319-30.
23) Stamler JS, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiological reviews. 2001; 81(1):209-37.
24) Chaubourt E, Voisin V, Fossier P, Baux G, Israël M, De La Porte S. Muscular nitric oxide synthase (muNOS) and utrophin. Journal of Physiology-Paris. 2002; 96(1):43-52.
25) Smith LW, Smith JD, Criswell DS. Involvement of nitric oxide synthase in skeletal muscle adaptation to chronic overload. Journal of Applied Physiology. 2002; 92(5): 2005-11.
26) Tews DS, Goebel HH, Schneider I, Gunkel A, Stennert E, Neiss WF. Expression of different isoforms of nitric oxide synthase in experimentally denervated and reinnervated skeletal muscle. Journal of neuropathology and experimental neurology. 1997; 56(12):1283.
27) Rubinstein I, Abassi Z, Coleman R, Milman F, Winaver J, Better OS. Involvement of nitric oxide system in experimental muscle crush injury. Journal of Clinical Investigation. 1998; 101(6):1325.
28) Richmonds CR, Boonyapisit K, Kusner LL, Kaminski HJ. Nitric oxide synthase in aging rat skeletal muscle. Mechanisms of ageing and development. 1999; 109(3):177-89.
29) Song W, Kwak HB, Kim JH, Lawler JM. Exercise training modulates the nitric oxide synthase profile in skeletal muscle from old rats. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2009; 64(5):540.
30) Nelson ME, Rejeski WJ, Blair SN, Duncan PW, Judge JO, King AC, et al. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Medicine and science in sports and exercise. 2007; 116 (9) 1094-105.
31) Naito H, Powers SK, Demirel HA, Aoki J. Exercise training increases heat shock protein in skeletal muscles of old rats. Medicine and science in sports and exercise. 2001; 33(5):729.
32) Hughes BW, Kusner LL, Kaminski HJ. Molecular architecture of the neuromuscular junction. Muscle & nerve. 2006; 33(4):445-61.
33) Desaulniers P, Lavoie PA, Gardiner PF. Endurance training increases acetylcholine receptor quantity at neuromuscular junctions of adult rat skeletal muscle. Neuroreport. 1998; 9(16):3549-52.
34) Andonian MH, Fahim MA. Effects of endurance exercise on the morphology of mouse neuromuscular junctions during ageing. Journal of neurocytology. 1987; 16(5):589-99.
35) Gharakhanlou R, Chadan S, Gardiner P. Increased activity in the form of endurance training increases calcitonin gene-related peptide content in lumbar motoneuron cell bodies and in sciatic nerve in the rat. Neuroscience. 1999; 89(4):1229-39.
36) Fernandez HL, Ross GS, Nadelhaft I. Neurogenic calcitonin gene-related peptide: a neurotrophic factor in the maintenance of acetylcholinesterase molecular forms in adult skeletal muscles. Brain research. 1999; 844(1):83-97.
37) 37.پرنو عبد الحسین, قراخانلو رضا, هدایتی مهدی, مهدیان رضا, گرگین زینب. اثر تمرینات ترکیبی و مقاومتی بر میزان پپتید وابسته به ژن کلسی تونین در عضلات کند و تند موش بالغ نژاد ویستار. دانشور. 1388؛ 16(84):11-1.
38) Huh K-H, Fuhrer C. Clustering of nicotinic acetylcholine receptors: from the neuromuscular junction to interneuronal synapses. Molecular neurobiology. 2002; 25(1):79-112.
39) Jones MA, Werle MJ. Nitric oxide is a downstream mediator of agrin-induced acetylcholine receptor aggregation. Molecular and Cellular Neuroscience. 2000; 16(5):649-60.
40) Pilgram GSK, Potikanond S, Baines RA, Fradkin LG, Noordermeer JN. The roles of the dystrophin-associated glycoprotein complex at the synapse. Molecular neurobiology. 2010; 41(1):1-21.
41) Lück G, Hoch W, Hopf C, Blottner D. Nitric oxide synthase (NOS-1) coclustered with agrin-induced AChR-specializations on cultured skeletal myotubes. Molecular and Cellular Neuroscience. 2000; 16(3):269-81.
42) Lau Kims, Grange RW, Isotani E, Sarelius IH, Kamm KE, Huang PL, et al. nNOS and eNOS modulate cGMP formation and vascular response in contracting fast-twitch skeletal muscle. Physiological genomics. 2000; 2(1):21-7.
43) Balon TW, Nadler JL. Evidence that nitric oxide increases glucose transport in skeletal muscle. Journal of Applied Physiology. 1997; 82(1):359-63.
44) Reiser PJ, Kline WO, Vaghy PL. Induction of neuronal type nitric oxide synthase in skeletal muscle by chronic electrical stimulation in vivo. Journal of Applied Physiology. 1997; 82(4):1250-5.
45) Roberts CK, Barnard RJ, Jasman A, Balon TW. Acute exercise increases nitric oxide synthase activity in skeletal muscle. American Journal of Physiology-Endocrinology And Metabolism. 1999; 277(2):390-4.
46) Tidball JG, Lavergne E, Lau KS, Spencer MJ, Stull JT, Wehling M. Mechanical loading regulates NOS expression and activity in developing and adult skeletal muscle. American Journal of Physiology-Cell Physiology. 1998; 275(1):260-6.
47) Kobzik L, Reid MB, Bredt DS, Stamler JS. Nitric oxide in skeletal muscle. Nature. 1994; 372(6506):546-8.
48) Kuru O, Şentürk ÜK, Koçer G, Özdem S, Başkurt OK, Cetin A, et al. Effect of exercise training on resistance arteries in rats with chronic NOS inhibition. Journal of Applied Physiology. 2009; 107(3):896-902.
49) Akimitsu T, Gute DC, Korthuis RJ. Leukocyte adhesion induced by inhibition of nitric oxide production in skeletal muscle. Journal of Applied Physiology. 1995; 78(5):1725-32.
50) Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell. 1994; 78(6):915-8.
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