The effect of 12 weeks aerobic training on TNF-α levels in the hippocampus and prefrontal cortex, and depression in rats with Alzheimer's disease
Subject Areas : Sport PhysiologyEhsan Mohammadikia 1 , Fereshteh Mohebbi 2 , Hossein Babaei 3
1 - Master of Applied Exercise Physiology, Payam Noor University Alborz – Karaj, Iran
2 - Phd Student of Sport Managment, Tarbiat modares university, Tehran,
3 - Master Student of Sport Managment, Tarbiat modares university, Tehran, Iran
Keywords: Alzheimer's, Exercise Training, Inflammation, Tumor Necrosis Factor ,
Abstract :
Background: Exercise training plays an important role in combating Alzheimer's disease. Present study aimed to investigate the effect of 12 weeks aerobic training on the levels of tumor necrosis factor alpha (TNF-α) in the hippocampus and prefrontal cortex, and also depression in rats with Alzheimer's disease. Methods: The 40 Wistar rats were divided into four equal groups including saline (S), saline +training (ST), training +STZ (AT) and STZ (A). Alzheimer's was induced by injection of 3 mg/kg streptozotocin (STZ) into the ventricles of brain. The aerobic training program (each session lasted 30 minutes with 10-12 meters per minute speed) performed for 12 weeks and five sessions per week on a treadmill. The 48 hours after last training session, brain tissue (hippocampal and prefrontal cortex areas) was removed and TNF-α levels were measured by ELISA method. Data were evaluated using the statistical method of analysis of variance at a significant level (P <0.05). Result: TNF-α levels in the hippocampus were significantly higher in group A compared to S (p= 0.010), ST (p= 0.014) and AT (p= 0.041) groups. Moreover, no significant change was observed for TNF-α levels in prefrontal cortex in different groups (p= 0.276). In addition, a significant increase in inactivity duration (FST) was observed in group A compared to other groups (p <0.05) and also a significant decrease in sucrose preference (SPT) was observed in group A compared to other groups. (p<0.05). Conclusion: The present study findings indicated that, the positive effects of aerobic training in rats with Alzheimer's disease are exerted partly by modulating the levels of inflammatory factors such as TNF-α in the brain especially the hippocampus.
1. Swarbrick S, Wragg N, Ghosh S, Stolzing A. Systematic Review of miRNA as Biomarkers in Alzheimer's Disease. Mol Neurobiol. 2019 Sep;56(9):6156-6167. doi: 10.1007/s12035-019-1500-y. Epub 2019 Feb 8. PMID: 30734227; PMCID: PMC6682547.
2. Hill E, Goodwill AM, Gorelik A, Szoeke C. Diet and biomarkers of Alzheimer's disease: a systematic review and meta-analysis. Neurobiol Aging. 2019 Apr;76:45-52. doi: 10.1016/j.neurobiolaging.2018.12.008. Epub 2018 Dec 27. PMID: 30682676.
3. Mucke L. Neuroscience: Alzheimer's disease. Nature. 2009 Oct 15;461(7266):895-7. doi: 10.1038/461895a. PMID: 19829367.
4. White JA, Manelli AM, Holmberg KH, Van Eldik LJ, Ladu MJ. Differential effects of oligomeric and fibrillar amyloid-beta 1-42 on astrocyte-mediated inflammation. Neurobiol Dis. 2005 Apr;18(3):459-65. doi: 10.1016/j.nbd.2004.12.013. PMID: 15755672.
5. Holmes C. Review: systemic inflammation and Alzheimer's disease. Neuropathol Appl Neurobiol. 2013 Feb;39(1):51-68. doi: 10.1111/j.1365-2990.2012.01307. x. PMID: 23046210.
6. Borish LC, Steinke JW. 2. Cytokines and chemokines. J Allergy Clin Immunol. 2003 Feb;111(2 Suppl): S460-75. doi: 10.1067/mai.2003.108. PMID: 12592293.
7. Nedoszytko B, Sokołowska-Wojdyło M, Ruckemann-Dziurdzińska K, Roszkiewicz J, Nowicki RJ. Chemokines and cytokines network in the pathogenesis of the inflammatory skin diseases: atopic dermatitis, psoriasis and skin mastocytosis. Postepy Dermatol Alergol. 2014 May;31(2):84-91. doi: 10.5114/pdia.2014.40920. Epub 2014 Apr 22. PMID: 25097473; PMCID: PMC4112246.
8. Prasad S, Sung B, Aggarwal BB. Age-associated chronic diseases require age-old medicine: role of chronic inflammation. Prev Med. 2012 May;54 Suppl (Suppl):S29-37. doi: 10.1016/j.ypmed.2011.11.011. Epub 2011 Dec 9. PMID: 22178471; PMCID: PMC3340492.
9. Huang WY, Wang J, Liu YM, Zheng QS, Li CY. Inhibitory effect of Malvidin on TNF-α-induced inflammatory response in endothelial cells. Eur J Pharmacol. 2014 Jan 15; 723:67-72. doi: 10.1016/j.ejphar.2013.11.041. Epub 2013 Dec 11. PMID: 24333549.
10. Du W, Erden O, Pang Q. TNF-α signaling in Fanconi anemia. Blood Cells Mol Dis. 2014 Jan;52(1):2-11. doi: 10.1016/j.bcmd.2013.06.005. Epub 2013 Jul 24. PMID: 23890415; PMCID: PMC3851925.
11. Ardebili SM, Yeghaneh T, Gharesouran J, Rezazadeh M, Farhoudi M, Ayromlou H, Talebi M, Ghojazadeh M. Genetic association of TNF-α-308 G/A and -863 C/A polymorphisms with late onset Alzheimer's disease in Azeri Turk population of Iran. J Res Med Sci. 2011 Aug;16(8):1006-13. PMID: 22279475; PMCID: PMC3263076.
12. Zhang YY, Fan YC, Wang M, Wang D, Li XH. Atorvastatin attenuates the production of IL-1β, IL-6, and TNF-α in the hippocampus of an amyloid β1-42-induced rat model of Alzheimer's disease. Clin Interv Aging. 2013; 8:103-10. doi: 10.2147/CIA.S40405. Epub 2013 Jan 31. PMID: 23386786; PMCID: PMC3563315.
13. Zhou M, Xu R, Kaelber DC, Gurney ME. Tumor Necrosis Factor (TNF) blocking agents are associated with lower risk for Alzheimer's disease in patients with rheumatoid arthritis and psoriasis. PLoS One. 2020 Mar 23;15(3):e0229819. doi: 10.1371/journal.pone.0229819. PMID: 32203525; PMCID: PMC7089534.
14. Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. 2011 Aug 5;11(9):607-15. doi: 10.1038/nri3041. PMID: 21818123.
15. Abraham D, Feher J, Scuderi GL, Szabo D, Dobolyi A, Cservenak M, Juhasz J, Ligeti B, Pongor S, Gomez-Cabrera MC, Vina J, Higuchi M, Suzuki K, Boldogh I, Radak Z. Exercise and probiotics attenuate the development of Alzheimer's disease in transgenic mice: Role of microbiome. Exp Gerontol. 2019 Jan; 115:122-131. doi: 10.1016/j.exger.2018.12.005. Epub 2018 Dec 6. PMID: 30529024.
16. Lovatel GA, Elsner VR, Bertoldi K, Vanzella C, Moysés Fdos S, Vizuete A, Spindler C, Cechinel LR, Netto CA, Muotri AR, Siqueira IR. Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus. Neurobiol Learn Mem. 2013 Mar; 101:94-102. doi: 10.1016/j.nlm.2013.01.007. Epub 2013 Jan 26. PMID: 23357282.
17. Bonifati DM, Kishore U. Role of complement in neurodegeneration and neuroinflammation. Mol Immunol. 2007 Feb;44(5):999-1010. doi: 10.1016/j.molimm.2006.03.007. Epub 2006 May 15. PMID: 16698083.
18. Belkhelfa M, Rafa H, Medjeber O, Arroul-Lammali A, Behairi N, Abada-Bendib M, Makrelouf M, Belarbi S, Masmoudi AN, Tazir M, Touil-Boukoffa C. IFN-γ and TNF-α are involved during Alzheimer disease progression and correlate with nitric oxide production: a study in Algerian patients. J Interferon Cytokine Res. 2014 Nov;34(11):839-47. doi: 10.1089/jir.2013.0085. Epub 2014 May 15. PMID: 24831467.
19. Flynn MG, McFarlin BK, Markofski MM. The Anti-Inflammatory Actions of Exercise Training. Am J Lifestyle Med. 2007 May;1(3):220-235. doi: 10.1177/1559827607300283. PMID: 25431545; PMCID: PMC4243532..
20. Souza LC, Filho CB, Goes AT, Fabbro LD, de Gomes MG, Savegnago L, Oliveira MS, Jesse CR. Neuroprotective effect of physical exercise in a mouse model of Alzheimer's disease induced by β-amyloid₁₋₄₀ peptide. Neurotox Res. 2013 Aug;24(2):148-63. doi: 10.1007/s12640-012-9373-0. Epub 2013 Jan 11. PMID: 23307759.
21. Nichol KE, Poon WW, Parachikova AI, Cribbs DH, Glabe CG, Cotman CW. Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid. J Neuroinflammation. 2008 Apr 9; 5:13. doi: 10.1186/1742-2094-5-13. PMID: 18400101; PMCID: PMC2329612.
22. Ding YH, Mrizek M, Lai Q, Wu Y, Reyes R Jr, Li J, Davis WW, Ding Y. Exercise preconditioning reduces brain damage and inhibits TNF-alpha receptor expression after hypoxia/reoxygenation: an in vivo and in vitro study. Curr Neurovasc Res. 2006 Nov;3(4):263-71. doi: 10.2174/156720206778792911. PMID: 17109621.
23. Chu WM. Tumor necrosis factor. Cancer Lett. 2013 Jan 28;328(2):222-5. doi: 10.1016/j.canlet.2012.10.014. Epub 2012 Oct 22. PMID: 23085193; PMCID: PMC3732748.
24. Lin JY, Kuo WW, Baskaran R, Kuo CH, Chen YA, Chen WS, Ho TJ, Day CH, Mahalakshmi B, Huang CY. Swimming exercise stimulates IGF1/ PI3K/Akt and AMPK/SIRT1/PGC1α survival signaling to suppress apoptosis and inflammation in aging hippocampus. Aging (Albany NY). 2020 Apr 22;12(8):6852-6864. doi: 10.18632/aging.103046. Epub 2020 Apr 22. Erratum in: Aging (Albany NY). 2020 Aug 30;12(16):16663-16664. PMID: 32320382; PMCID: PMC7202519.
25. Sun LN, Qi JS, Gao R. Physical exercise reserved amyloid-beta induced brain dysfunctions by regulating hippocampal neurogenesis and inflammatory response via MAPK signaling. Brain Res. 2018 Oct 15; 1697:1-9. doi: 10.1016/j.brainres.2018.04.040. Epub 2018 May 2. PMID: 29729254.
26. Afzalpour ME, Chadorneshin HT, Foadoddini M, Eivari HA. Comparing interval and continuous exercise training regimens on neurotrophic factors in rat brain. Physiol Behav. 2015 Aug 1; 147:78-83. doi: 10.1016/j.physbeh.2015.04.012. Epub 2015 Apr 11. PMID: 25868740.
27. Guo M, Lin V, Davis W, Huang T, Carranza A, Sprague S, Reyes R, Jimenez D, Ding Y. Preischemic induction of TNF-alpha by physical exercise reduces blood-brain barrier dysfunction in stroke. J Cereb Blood Flow Metab. 2008 Aug;28(8):1422-30. doi: 10.1038/jcbfm.2008.29. Epub 2008 Apr 16. PMID: 18414498.