The Effect of Eight Weeks of Taking a Combined Supplement with Aerobic Exercise on Hippocampal ARC and IGF-1 Gene Expression and Cognitive Performance in Rats with Alzheimer's Disease: An Experimental Study

Document Type : Original Articles

Authors
1 PhD Student, Department of Exercise Physiology, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran
2 Associate Professor, Department of Exercise Physiology, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran
3 Professor, Department of Exercise Physiology, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran
10.48305/jrrs.2023.42150.1068
Abstract
Introduction: ARC and IGF-1 are important molecular markers for brain neurogenesis, which are significantly reduced in brain tissue in various conditions such as Alzheimer's. The aim of this study was to investigate the effect of eight weeks of consuming combined supplement in conjunction with aerobic exercise on hippocampal ARC and IGF-1 gene expression and cognitive function in elderly rats with Alzheimer's disease.
Material and Methods: In this experimental study, 25 male c57 mice with Alzheimer's (age: 14-16 weeks, weight: 30-35 grams), were randomly divided into healthy control groups, Alzheimer's, Alzheimer's + aerobic exercise, Alzheimer's + combined supplement, Alzheimer's + aerobic exercise + combined supplement. Alzheimer's induction was performed by injecting amyloid beta-42 (Aβ1) into the hippocampus. The aerobic exercise protocol was five days per week for eight weeks before and after Alzheimer's induction. Kibi's supplement of resveratrol with a concentration of 25 mg/kg and fisetin with a concentration of 20 mg/kg was used for eight weeks. To analyze the data, one-way analysis of variance and Tukey's post hoc test were used at a significance level of 0.05.
Results: Alzheimer's induction caused a significant decrease in the expression of ARC and IGF-1 gene (P = 0.001), a significant increase in the expression of the APP gene in the hippocampus (P = 0.001) and a significant decrease in the cognitive function of the hippocampus (P = 0.001). Aerobic exercise and combined supplement use separately and simultaneously caused significant improvement of all the above changes (P=0.001).
Conclusion: It seems that aerobic exercise and taking a combined supplement can probably help to increase brain neurogenesis and improve cognitive function in elderly people with Alzheimer's through increasing the expression of ARC and IGF-1 in the hippocampus.
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1.     Vieweg J, Panzer S, Schaefer S. Effects of age simulation and age on motor sequence learning: Interaction of age-related cognitive and motor decline. Human Movement Science. 2023; 1; 87: 103025.
2.     Bacanoiu MV, Danoiu M. New strategies to improve the quality of life for normal aging versus pathological aging. Journal of Clinical Medicine. 2022; 20; 11(14): 4207.
3.     Poirier G, Ohayon A, Juranville A, Mourey F, Gaveau J. Deterioration, compensation and motor control processes in healthy aging, mild cognitive impairment and Alzheimer’sdisease. Geriatrics. 2021; 6(1): 33.
4.     Khaledi S, Ahmadi S. Amyloid Beta and Tau: From Physiology to Pathology in Alzheimer’s Disease.Neurosci J Shefaye Khatam 2016; 4(4): 67-88. [In Persian].
5.     Sehar U, Rawat P, Reddy AP, Kopel J, Reddy PH. Amyloid beta in aging and Alzheimer’s disease. International journal of molecular sciences. 2022; 26; 23(21): 12924.
6.     Mandal PK, Roy RG, Samkaria A. Oxidative Stress: Glutathione and Its Potential to Protect Methionine-35 of Aβ Peptide from Oxidation. Acs Omega. 2022; 26; 7(31): 27052-61.
7.     Doros tkar MM, Zou C, Blazquez-Llorca L, Herms J. Analyzing dendritic spine pathology in Alzheimer’s disease: problems and opportunities. Acta Neuropathol. 2015; 130(1): 1-19.
8.     Manocha GD, Floden AM, Rausch K, Kulas JA, McGregor BA, Rojanathammanee L, et al. APP regulates microglial phenotype in a mouse model of Alzheimer’s disease. J Neurosci. 2016; 36(32): 8471-86.
9.     Zheng F, Luo Y, Wang H. Regulation of BDNF-mediated transcription of immediate early gene Arc by intracellular calcium and calmodulin. Journal of neuroscience research. 2009; 87(2): 380.
10.  Bramham CR, Worley PF, Moore MJ, et al. The immediate early gene Arc/Arg3.1: regulation, mechanisms, and function. The Journal of Neuroscience 2008; 1228(46): 11760-7.
11.  Wang Z, Tan L, Zong Y, Ma YH, Wang ZB, Wang HF, Tan L. sTREM2 and GFAP Mediated the Association of IGF-1 Signaling Biomarkers with Alzheimer’s Disease Pathology. Journal of Alzheimer's Disease. 2023 (Preprint): 1-7.
12.  Gaitán JM, Moon HY, Stremlau M, Dubal DB, Cook DB, Okonkwo OC, Van Praag H. Effects of aerobic exercise training on systemic biomarkers and cognition in late middle-aged adults at risk for Alzheimer’s disease. Frontiers in Endocrinology. 2021; 20; 12: 660181.
13.  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.
14.  Mehrabi A, Gaeini A, Nouri R, Daryanoosh F. The effect of six-week HIIT swimming exercise and Resveratrol supplementation on the level of SIRT3 in frontal lobe of aged rats. The Neuroscience Journal of Shefaye Khatam. 2021; 10; 9(2): 48-59.
15.  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(3): 2269-85.
16.  Elsallabi O, Patruno A, Pesce M, Cataldi A, Carradori S, Gallorini M. Fisetin as a senotherapeutic agent: biopharmaceutical properties and crosstalk between cell senescence and neuroprotection. Molecules. 2022; 23; 27(3): 738.
17.  Mizui T, Ishikawa Y, Kumanogoh H, Lume M, Matsumoto T, Hara T, et al. BDNF pro-peptide actions facilitate hippocampal LTD and are altered by the common BDNF polymorphism Val66Met. Proc Natl Acad Sci USA 2015; 112(23): E3067-74
18.  Palop JJ, Chin J, Bien-Ly N, Massaro C, Yeung BZ, Yu GQ, Mucke L. Vulnerability of dentate granule cells to disruption of arc expression in human amyloid precursor protein transgenic mice. J Neurosci Res. 2005;19; 25(42): 9686-93
19.  Shamsipour S, Sharifi G, Taghian F. Impact of interval training with probiotic (L. plantarum/Bifidobacterium bifidum) on passive avoidance test, ChAT and BDNF in the hippocampus of rats with Alzheimer's disease. Neurosci Lett. 2021; 21; 756: 135949
20.  Qarari R, Saqib Jo M, Hedayati M, Fathi, R. The effect of aerobic exercise and omega-3 consumption on brain-derived neurotrophic factor in the hippocampus of male Alzheimer's rats treated with homocysteine. Sci J Kurdistan Uni Med Sci. 2016; 10; 21(2): 53-64
21.  Leung HW, Foo G, VanDongen A. Arc regulates transcription of genes for plasticity, excitability and Alzheimer’s disease. Biomedicines. 2022; 11; 10(8): 1946.
22.  Kaushik M, Kaushik P, Parvez S. Memory related molecular signatures: The pivots for memory consolidation and Alzheimer's related memory decline. Ageing Res Rev. 2022; 29: 101577.
23.  López-Ortiz S, Lista S, Valenzuela PL, Pinto-Fraga J, Carmona R, Caraci F, Caruso G, Toschi N, Emanuele E, Gabelle A, Nisticò R. Effects of physical activity and exercise interventions on Alzheimer's disease: an umbrella review of existing meta-analyses. J Neurol. 2023; 270(2): 711-25
24.  Arnarson A, Gudny Geirsdottir O, Ramel A, Jonsson PV, Thorsdottir I. Insulin-like growth factor-1 and resistance exercise in community dwelling old adults. The Journal of Nutrition, Health and Aging. 2015; 19(8): 856-60
25.  Farooqui T, Farooqui AA. Diet and exercise in cognitive function and neurological diseases. Hoboken: Wiley‐Blackwell; 2015.
26.  Maass A, Düzel S, Brigadski T, Goerke M, Becke A, Sobieray U, et al. Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults. NeuroImage. 2016; 131: 142-54.
27.  Duzel E, van Praag H, Sendtner M. Can physical exercise in old age improve memory and hippocampal function? Brain. 2016; 139(3): 662-73.
28.  Bhalla S, Mehan S, Khan A, Rehman MU. Protective role of IGF-1 and GLP-1 signaling activation in neurological dysfunctions. Neuroscience & Biobehavioral Reviews. 2022: 104896.
29.  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.
30. Tosatti JA, Fontes AF, Caramelli P, Gomes KB. Effects of resveratrol supplementation on the cognitive function of patients with Alzheimer's disease: a systematic review of randomized controlled trials. Drugs & Aging. 2022; 39(4): 285-95.