The Effect of Eight Weeks of Progressive Aerobic Training and Fisetin Supplementation on TGFβ and FGF2 Gene Expression in Aged Mice with Alzheimer's Disease

Jalali Dehkordi,  A; Azamian Jazi,  A; Jalali Dehkordi , Kh

[Home ] [Archive]

[ فارسی ]

Main Menu

Home

Journal Information

Articles archive

For Authors

For Reviewers

Registration

Contact us

Site Facilities

Indexing & Abstracting

Publication Ethics

Search in website

Receive site information

Indexing & Abstracting

DOAJ
GOOGLE SCHOLAR

Volume 30, Issue 2 (2-2025)

__Armaghane Danesh__ 2025, 30(2): 136-149

Back to browse issues page

The Effect of Eight Weeks of Progressive Aerobic Training and Fisetin Supplementation on TGFβ and FGF2 Gene Expression in Aged Mice with Alzheimer's Disease

A Jalali Dehkordi¹

, A Azamian Jazi²

, Kh Jalali Dehkordi³

1- Department of Sport Sciences, Shahrekord University, Shahrekord, Iran
2- Department of Sport Sciences, Shahrekord University, Shahrekord, Iran , azamianakbar@yahoo.com
3- Department of Sport Physiology, Isfahan(Khorasgan) Branch, Islamic Azad University, Isfahan, Iran

Abstract: (1900 Views)

Background & aim: TGFβ and FGF2 are important molecular markers for cerebral angiogenesis, which are significantly reduced in Alzheimer's disease (AD) in brain tissue and may be affected by exercise training. Therefore, the present study aimed to investigate the effect of eight weeks of progressive aerobic training and fisetin supplementation on TGFβ and FGF2 gene expression in aged mice with AD.

Methods: In the present experimental study conducted in 2023, thirty healthy elderly male C57BL/6 mice with Alzheimer's disease (AD) were equally divided into five groups, including: healthy control, Alzheimer's (AD), AD + Fisetin, AD + Aerobic Training (AT), and AD + AT + Fisetin. Rats of AD groups developed AD by injecting amyloid beta (Aβ1-42) into the hippocampus. Aerobic training protocol started five days a week for eight weeks with zero slope and a speed of 10 meters per minute for 30 minutes and reached 27 meters per minute for 40 minutes in the eighth week. A fisetin supplement, with a concentration of 20 mg/kg, was used for eight weeks. Data analysis was performed using a one-way analysis of variance and Tukey's post hoc test (P≥0.05).

Results: The changes in the expression of TGF-β and FGF2 genes in the brain tissue of aged mice were significantly different among the five groups (P<0.01), and also based on the results of the post hoc test, their expression in the AD groups decreased significantly (P<0.01) compared to the healthy control group. Also, their expression increased significantly in AD + exercise + fisetin, AD + exercise, and AD + fisetin groups compared to AD group (P<0.01). In addition, their expression in the AD + exercise + fisetin group was significantly higher than the AD + exercise and also their expression was significantly higher in the AD + exercise group than in the AD + fisetin group (P<0.01).

Conclusion: It seems that the combination of progressive aerobic training and fisetin supplement, or each of them alone, can help to increase cerebral angiogenesis in patients with Alzheimer's disease, maybe through increasing the expression of TGFβ and FGF2. Of course, the combination of fisetin and aerobic training has a more significant effect than aerobic training and supplementation alone, and aerobic training is more effective than taking fisetin alone. Therefore, the combination of progressive aerobic training and fisetin is recommended as the most effective complementary treatment method for this disease.

Keywords: Exercise, Angiogenesis, Dietary Supplements, Alzheimer Disease

Full-Text [PDF 648 kb] (31 Downloads)

Type of Study: Research | Subject: Sport Physiology
Received: 2024/07/30 | Accepted: 2024/09/29 | Published: 2025/02/4

References

1. Maher P. Fisetin acts on multiple pathways to reduce the impact of age and disease on CNS function. Frontiers in bioscience 2015; 7: 58.## [DOI:10.2741/s425] [PMID] []

2. Abraham D, Feher J, Scuderi GL, Szabo D, Dobolyi A, Cservenak M, et al. Exercise and probiotics attenuate the development of Alzheimer's disease in transgenic mice: role of microbiome. Experimental Gerontology 2019; 115: 122-31. ## [DOI:10.1016/j.exger.2018.12.005] [PMID]

3. Li MO, Sanjabi S, Flavell RA. Transforming growth factor-β controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and-independent mechanisms. Immunity 2006; 25(3): 455-71. ## [DOI:10.1016/j.immuni.2006.07.011] [PMID]

4. Sousa VDO, Almeida JC, Eller CM, Alcantara Comes FC. Characterization of TGF-β1 type II receptor expression in cultured cortical astrocytes. In Vitro Cellular & Developmental Biology-Animal 2006; 42: 171-5. ## [DOI:10.1290/0602013.1] [PMID]

5. Chalmers KA, Love S. Neurofibrillary tangles may interfere with Smad 2/3 signaling in neurons. Journal of Neuropathology & Experimental Neurology 2007; 66(2): 158-67. ## [DOI:10.1097/nen.0b013e3180303b93] [PMID]

6. Fakhraei S, Almasi MR, Peeri M, Gharakhanlou R. The effect of 4-Week rehabilitation by aerobic exercise on hippocampus BDNF and TGF-β1 gene expressions in Aβ 1-42-induced rat model of Alzheimer's disease. Journal of Clinical Neuroscience 2022; 95: 106-11. ## [DOI:10.1016/j.jocn.2021.11.027] [PMID]

7. Tesseur I, Zou K, Esposito L, Bard F, Berber E, Van Can J, et al. Deficiency in neuronal TGF-β signaling promotes neurodegeneration and Alzheimer's pathology. The Journal of Clinical Investigation 2006; 116(11): 3060-9. ## [DOI:10.1172/JCI27341] [PMID] []

8. Li XX, Cai ZP, Lang XY, Pan RY, Ren TT, Lan R, et al. Coeloglossum viride var. bracteatum extract improves cognitive deficits by restoring BDNF, FGF2 levels and suppressing RIP1/RIP3/MLKL-mediated neuroinflammation in a 5xFAD mouse model of Alzheimer's disease. Journal of Functional Foods 2021; 85: 104612. ## [DOI:10.1016/j.jff.2021.104612]

9. Tsai CL, Pai MC, Ukropec J, Ukropcová B. Distinctive effects of aerobic and resistance exercise modes on neurocognitive and biochemical changes in individuals with mild cognitive impairment. Current Alzheimer Research 2019; 16(4): 316-32. ## [DOI:10.2174/1567205016666190228125429] [PMID]

10. Kashef M, Salehpour M, Sadegh Ghomi M. Effect of eight weeks swimming exercise training on VEGF-A and FGF-2 of hippocampus tissue and Lee's index in male wistar rats. Journal of Sport and Biomotor Sciences 2019; 22(22): 10-8. ##

11. Debove L, Bru N, Couderc M, Noé F, Paillard T. Physical activity limits the effects of age and Alzheimer's disease on postural control. Neurophysiologie Clinique/Clinical Neurophysiology 2017; 47(4): 301-4. ## [DOI:10.1016/j.neucli.2017.03.005] [PMID]

12. Abdullahi A, Wong TW-L, Ng SS-M. Understanding the mechanisms of disease modifying effects of aerobic exercise in people with Alzheimer's disease. Ageing Research Reviews 2024; 1(94): 1-13. ## [DOI:10.1016/j.arr.2024.102202] [PMID]

13. Atri A. The Alzheimer's disease clinical spectrum: diagnosis and management. Medical Clinics 2019; 103(2): 263-93. ## [DOI:10.1016/j.mcna.2018.10.009] [PMID]

14. Puoyan-Majd S, Parnow A, Rashno M, Heidarimoghadam R, Komaki A. The protective effects of high-intensity interval training combined with q10 supplementation on learning and memory impairments in male rats with amyloid-β-induced alzheimer's disease. Journal of Alzheimer's Disease 2024; 99(s1): S67-80. ## [DOI:10.3233/JAD-230096] [PMID]

15. Montero-Odasso M, Zou G, Speechley M, Almeida QJ, Liu-Ambrose T, Middleton LE, et al. Effects of exercise alone or combined with cognitive training and vitamin D supplementation to improve cognition in adults with mild cognitive impairment: a randomized clinical trial. JAMA Network Open 2023; 6(7): e2324465. ## [DOI:10.1001/jamanetworkopen.2023.24465] [PMID] []

16. Nameni F, Rasoli Z. Investigating the effects of melilot extract and resistance training on protein expression APP in the hippocampus of Alzheimer's model rats. Sport Physiology & Management Investigations 2024; 15(4): 195-297. ##

17. Ahmad A, Ali T, Park HY, Badshah H, Rehman SU, Kim MO. Neuroprotective effect of fisetin against amyloid-beta-induced cognitive/synaptic dysfunction, neuroinflammation, and neurodegeneration in adult mice. Molecular Neurobiology 2017; 54: 2269-85. ## [DOI:10.1007/s12035-016-9795-4] [PMID]

18. Wang Y, Wu X, Ren W, Liu Y, Dai X, Wang S, et al. Protective effects of fisetin in an Aβ1-42-induced rat model of Alzheimer's disease. Folia Neuropathologica 2023; 61(2): 196-208. ## [DOI:10.5114/fn.2023.126893] [PMID]

19. Yang L, Wang Y, Li Z, Wu X, Mei J, Zheng G. Brain targeted peptide-functionalized chitosan nanoparticles for resveratrol delivery: impact on insulin resistance and gut microbiota in obesity-related Alzheimer's disease. Carbohydrate Polymers 2023; 310: 120714. ## [DOI:10.1016/j.carbpol.2023.120714] [PMID]

20. Fathi A, Namvar S. Six weeks of continuous aerobic training increases the neuronal density in the CA1 area of the hippocampus and improves memory performance in aged AD model rats. Metabolism and Exercise 2021; 11(2): 113-28. ##

21. Ten Dijke P, Hill CS. New insights into TGF-β-Smad signalling. Trends in Biochemical Sciences 2004; 29(5): 265-73. ## [DOI:10.1016/j.tibs.2004.03.008] [PMID]

22. Güven G, Köseoğlu P, Lohmann E, Samancı B, Şahin E, Bilgiç B, et al. Peripheral Expression of IL-6, TNF-α and TGF-β1 in Alzheimer's Disease Patients. Turkish Journal of Immunology 2024; 12(1): 28-34. ## [DOI:10.4274/tji.galenos.2024.76598]

23. Tesseur I, Nguyen A, Chang B, Li L, Woodling NS, Wyss-Coray T, et al. Deficiency in neuronal TGF-β signaling leads to nigrostriatal degeneration and activation of TGF-β signaling protects against MPTP neurotoxicity in mice. Journal of Neuroscience 2017; 37(17): 4584-92. ## [DOI:10.1523/JNEUROSCI.2952-16.2017] [PMID] []

24. Kapoor M, Chinnathambi S. TGF-β1 signalling in alzheimer's pathology and cytoskeletal reorganization: a specialized tau perspective. Journal of Neuroinflammation 2023; 20(1): 72. ## [DOI:10.1186/s12974-023-02751-8] [PMID] []

25. Hiew LF, Poon CH, You HZ, Lim LW. TGF-β/Smad signalling in neurogenesis: implications for neuropsychiatric diseases. Cells 2021; 10(6): 1382. ## [DOI:10.3390/cells10061382] [PMID] []

26. Eslami A, Habibian M, Farzanegi P. Effect of swimming exercise and garlic extract consumption on some of growth factors involved in angiogenesis and neurogenesis in the brain tissue of old rats. Daneshvar Med 2016; 23(121): 13-20. ##

27. Soltani M, Fathi M, Moazzemi M, Golradi N. The effects of aerobic exercise in water on cortisol levels and TGF-β in patients with multiple sclerosis. Journal of Sabzevar University of Medical Sciences 2014; 21(2): 207-16. ##

28. Hanneken A, Frautschy S, Galasko D, Baird A. A fibroblast growth factor binding protein in human cerebral spinal fluid. Neuroreport 1995; 6(6): 886-8. ## [DOI:10.1097/00001756-199504190-00015] [PMID]

29. Kole D, Grella A, Dolivo D, Shumaker L, Hermans W, Dominko T. High molecular weight FGF2 isoforms demonstrate canonical receptor-mediated activity and support human embryonic stem cell self-renewal. Stem Cell Research 2017; 21: 106-16. ## [DOI:10.1016/j.scr.2017.04.006] [PMID] []

30. Xie X, Zhang X, Li S, Du W. Involvement of Fgf2-mediated tau protein phosphorylation in cognitive deficits induced by sevoflurane in aged rats. Molecular Medicine 2024; 30(1): 39. ## [DOI:10.1186/s10020-024-00784-0] [PMID] []

31. Alam R, Mrad Y, Hammoud H, Saker Z, Fares Y, Estephan E, et al. New insights into the role of fibroblast growth factors in Alzheimer's disease. Molecular Biology Reports. 2022; 1(49): 1413-1427. ## [DOI:10.1007/s11033-021-06890-0] [PMID]

32. Zhao R. Can exercise benefits be harnessed with drugs? A new way to combat neurodegenerative diseases by boosting neurogenesis. Translational Neurodegeneration 2024; 13(1): 1-28. ## [DOI:10.1186/s40035-024-00428-7] [PMID] []

33. Huang S, Mao J, Ding K, Zhou Y, Zeng X, Yang W, et al. Polysaccharides from Ganoderma lucidum promote cognitive function and neural progenitor proliferation in mouse model of Alzheimer's disease. Stem Cell Reports 2017; 8(1): 84-94. ## [DOI:10.1016/j.stemcr.2016.12.007] [PMID] []

34. Kiyota T, Ingraham KL, Jacobsen MT, Xiong H, Ikezu T. FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders. Proceedings of the National Academy of Sciences 2011; 108(49): E1339-E48. ## [DOI:10.1073/pnas.1102349108] [PMID] []

35. Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, Aisen PS, et al. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease. Journal of Neuroinflammation 2017; 14: 1-10. ## [DOI:10.1186/s12974-016-0779-0] [PMID] []

36. Abdullahzadeh M, Nobejari M, Abdoli B, Rana Fayaz Milani R. The effect of aerobic exercise along with living in enriched environment on spatial memory and brain-derived neurotrophic factor in the Hippocampal tissue of Elderly female Wistar rats with Alzheimer's disease. Journal of Sport and Exercise Physiology 2024; 17(1): 29-44. ##

37. Wu CW, Chen YC, Yu L, Chen Hi, Jen CJ, Huang AM, et al. Treadmill exercise counteracts the suppressive effects of peripheral lipopolysaccharide on hippocampal neurogenesis and learning and memory. Journal of Neurochemistry 2007; 103(6): 2471-81. ## [DOI:10.1111/j.1471-4159.2007.04987.x] [PMID]

38. Gómez-Pinilla F, Dao L, So V. Physical exercise induces FGF-2 and its mRNA in the hippocampus. Brain Research 1997; 764(1-2): 1-8. ## [DOI:10.1016/S0006-8993(97)00375-2] [PMID]

39. Nabizadeh F. Neuroprotective role of Fisetin in Alzheimer's disease: An overview of potential mechanism and clinical findings. Neurology Letters 2024; 3(Special Issue (Diagnostic and Therapeutic advances in Neurodegenerative diseases)): 14-25. ## [DOI:10.61186/nl.3.2.14]

Send email to the article author

Add your comments about this article

Mendeley

Zotero

RefWorks

Jalali Dehkordi A, Azamian Jazi A, Jalali Dehkordi K. The Effect of Eight Weeks of Progressive Aerobic Training and Fisetin Supplementation on TGFβ and FGF2 Gene Expression in Aged Mice with Alzheimer's Disease. armaghanj 2025; 30 (2) :136-149
URL: http://armaghanj.yums.ac.ir/article-1-3661-en.html

Rights and permissions
	This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Volume 30, Issue 2 (2-2025)

Back to browse issues page

Persian site map - English site map - Created in 0.11 seconds with 37 queries by YEKTAWEB 4725