Document Type : Research Paper I Open Access I Released under (CC BY-NC) license

Authors

1 Kish International Campus of Tehran University

2 Department of Exercise Physiology, Faculty of Sport Sciences and Health, University of Tehran, Tehran, Iran

Abstract

Introduction: The aim of the present research was to compare the effects of four weeks of aerobic exercise (swimming) and resistance exercise (climbing stairs) on the levels of Sirtuin-1 protein (SIRT1) and Nicotinamide Adenine Dinucleotide (NAD+) in the brain in the chronic experimental autoimmune encephalomyelitis (EAE) period. Methodology: This study was conducted using a laboratory method. 40 female C57BL6 mice, 8 weeks old with an average weight of 18±2 grams, were selected for the experiment. For the experiment process, the sample group members were divided into four groups: healthy control, EAE, EAE + swimming, and EAE + resistance exercise. After inducing EAE with MOG35-33, the exercise groups performed swimming and resistance exercise programs for 30 minutes, 5 days a week for 4 weeks. On the 30th day post-induction (chronic disease period), the mice were anesthetized with ketamine and xylazine, followed by brain dissection and tissue sampling. The levels of SIRT1 and NAD+ proteins were measured using immunohistochemistry. One-way analysis of variance (ANOVA) was used to compare the research groups. Tukey's post hoc test was used to compare differences between groups. Results: The findings of the current research showed that both swimming and resistance exercises significantly increased the levels of NAD+ and SIRT1 proteins compared to the EAE group, although resistance exercise was more effective than swimming (P ≤ 0.05). Conclusion: Exercise, especially resistance exercise, may reduce disease progression in EAE by increasing NAD+ and SIRT1 levels.

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Main Subjects

.        Zhang, Y., et al., Review of the anti-inflammatory effect of SIRT1 and SIRT2 modulators on neurodegenerative diseases. Eur J Pharmacol, 2020. 867: p. 172847.
2.             Zhang, F., et al., Protective effects and mechanisms of sirtuins in the nervous system. Prog Neurobiol, 2011. 95(3): p. 373-95.
3.             Nimmagadda, V.K., et al., Overexpression of SIRT1 protein in neurons protects against experimental autoimmune encephalomyelitis through activation of multiple SIRT1 targets. J Immunol, 2013. 190(9): p. 4595-607.
4.             Tegla, C.A., et al., SIRT1 is decreased during relapses in patients with multiple sclerosis. Exp Mol Pathol, 2014. 96(2): p. 139-48.
5.             Hoseini, S.M., Z. Falah Mohammadi, and V. Talebi, Preventive Effect six Weeks of Swimming Training on the Levels of Cytokines and Brain-Derived Neurotrophic Rat Model of EAE. Journal of Sport Biosciences, 2020. 12(1): p. 53-65.
6.             Nazari, M., et al., Ameliorating effect of 6-week swimming exercise on mice with experimental autoimmune encephalomyelitis (EAE) by reducing fetuin-A and increasing AMPK & NAD(⁺) levels in liver tissue. Iran J Basic Med Sci, 2022. 25(8): p. 1016-1020.
7.             Huang, J., et al., Exercise activates lysosomal function in the brain through AMPK-SIRT1-TFEB pathway. CNS Neurosci Ther, 2019. 25(6): p. 796-807.
8.             Souza, P.S., et al., Physical Exercise Attenuates Experimental Autoimmune Encephalomyelitis by Inhibiting Peripheral Immune Response and Blood-Brain Barrier Disruption. Mol Neurobiol, 2017. 54(6): p. 4723-4737.
9.             Li, R., et al., Serum CCL20 and its association with SIRT1 activity in multiple sclerosis patients. Journal of neuroimmunology, 2017. 313: p. 56-60.
10.           Nimmagadda, V.K., et al., Overexpression of SIRT1 protein in neurons protects against experimental autoimmune encephalomyelitis through activation of multiple SIRT1 targets. The Journal of Immunology, 2013. 190(9): p. 4595-4607.
11.           Wang, J., et al., Treatment with NAD(+) inhibited experimental autoimmune encephalomyelitis by activating AMPK/SIRT1 signaling pathway and modulating Th1/Th17 immune responses in mice. Int Immunopharmacol, 2016. 39: p. 287-294.
12.           Saffar Kohneh Quchan, A.H., et al., Voluntary wheel running stimulates the expression of Nrf-2 and interleukin-10 but suppresses interleukin-17 in experimental autoimmune encephalomyelitis. Neuroscience Letters, 2020. 738: p. 135382.
13.           Mohammadi, G., m. kordi, and S. Choobineh, The effect of four weeks of physical activity in the enriched environment on inflammatory and anti-inflammatory factors in the dorsal horn of the spinal cord of mice with experimental autoimmune encephalomyelitis. Journal of Applied Health Studies in Sport Physiology, 2022. 9(2): p. 138-148.
14.           Huang, W.J., X. Zhang, and W.W. Chen, Gaucher disease: a lysosomal neurodegenerative disorder. Eur Rev Med Pharmacol Sci, 2015. 19(7): p. 1219-26.
15.           Martini-Stoica, H., et al., The Autophagy-Lysosomal Pathway in Neurodegeneration: A TFEB Perspective. Trends Neurosci, 2016. 39(4): p. 221-234.
16.           Kim, J., et al., AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol, 2011. 13(2): p. 132-41.
17.           Gailite, I., B.L. Aerne, and N. Tapon, Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system. Proc Natl Acad Sci U S A, 2015. 112(37): p. E5169-78.
18.           Salminen, A. and K. Kaarniranta, SIRT1: regulation of longevity via autophagy. Cell Signal, 2009. 21(9): p. 1356-60.
19.           Cantó, C., et al., AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature, 2009. 458(7241): p. 1056-60.
20.           Chen, Z., et al., Shear stress, SIRT1, and vascular homeostasis. Proc Natl Acad Sci U S A, 2010. 107(22): p. 10268-73.