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Volume 15, Issue 4 (1-2026)                   cmja 2026, 15(4): 301-310 | Back to browse issues page

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Janbarari F Z, Taghipoor A, Farajtabar Behrestaq S, Mousavi Amin M. Protective Effect of Interval Training Combined with Resveratrol Consumption on Hippocampal γ and β Secretase Expression in Alzheimer's Rats with Beta Amyloid. cmja 2026; 15 (4) :301-310
URL: http://cmja.arakmu.ac.ir/article-1-1049-en.html
Protective Effect of Interval Training Combined with Resveratrol Consumption on Hippocampal γ and β Secretase Expression in Alzheimer's Rats with Beta Amyloid
Fatemeh Zahra Janbarari1 , Amir Taghipoor *2 , Saqqa Farajtabar Behrestaq1 , Mohsen Mousavi Amin1
1- Department of Physical Education and Sport Sciences, QaS.C., Islamic Azad University, Qaemshahr, Iran
2- Department of Physical Education and Sport Sciences, QaS.C., Islamic Azad University, Qaemshahr, Iran , amir.taghipoor@iau.ac.ir
Keywords: Alzheimer's disease, Hippocampus, Interval training, Resveratrol, Secretase
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INTRODUCTION

Alzheimer's (AD) disease is characterized by the accumulation of amyloid-beta plaques, particularly in the hippocampus (2). These accumulations damage neuronal function, leading to the development of cognitive and behavioral symptoms of the disease (3). All of these changes contribute to the memory loss common in old age, ischemia, and AD (4). Accumulation of β-amyloid peptide (Aβ) in the brain is a major hallmark of sporadic and familial forms of AD (5). The Aβ is cleaved from APP (Amyloid Precursor Protein) by β-secretase 1 (BACE1) and subsequently by γ-secretase. The γ-secretase is a plasma membrane-embedded complex composed of at least four proteins: presenilin-1 (PS1), nicastrin (NCT), anterior pharyngeal phenotype defect, and presenilin enhancer 2. The PS1, an aspartyl protease, is the catalytic subunit of the γ-secretase complex, mediating the intramembrane proteolysis of APP and other transmembrane proteins, including Notch and cadherins. Cleavage of these proteins by γ-secretase releases active cytoplasmic peptide fragments that have important biological functions (9). β-Secretase, widely known as the amyloid beta-site precursor protein cleaving enzyme (BACE1), initiates the production of Aβ, which plays an important early role in the pathogenesis of Alzheimer's disease (10). Physical exercise is associated with neuroprotection and is considered as a protective and therapeutic strategy in the management of cognitive impairments and neurological disorders, through various proposed beneficial effects on neuronal survival, neuroinflammation, vascularization, and brain amyloid burden (12). Epidemiological findings suggest that regular exercise can reduce the risk of AD, and studies in mouse models of AD have shown that exercise on a running wheel can reduce Aβ accumulation and improve cognitive deficits (13). Resveratrol (RSV) is a natural polyphenol with potent effects, including antioxidative, anti-inflammatory, cardiovascular protective, neuroprotective, and cancer preventive activities (18). It has been suggested that RSV may act as a potent antioxidant in neurodegenerative disorders. Previous studies have reported that RSV has the ability to regulate Aβ toxicity or significantly increase the rate of Aβ clearance in a mouse model of AD (19). The Aβ accumulation in the brain induces cytotoxicity, apoptosis, and activation of astrocytes in cellular and animal models (25). Therefore, in this study, we investigated the protective effect of interval training combined with RSVconsumption on hippocampal γ and β secretase expression in Alzheimer's rats with beta amyloid.

METHODS

To conduct the present experimental study, 35 8-week-old male Wistar rats with an average weight of 223.17 ± 9.08 g were obtained from the Pasteur Institute and transferred to the laboratory with free access to water and special rat food to familiarize them with the new environment. After adaptation to the new environmental conditions (after one week), the rats were divided into five groups of eight: normal (NO), Alzheimer (AD), Alzheimer-training (ADT), Alzheimer-resveratrol (ADRSV), and Alzheimer-training-resveratrol (ADTRSV) (26). To induce Alzheimer's disease, amyloid beta 42-1 was purchased from Sigma-Aldrich. Resveratrol (20 mg/kg from Sigma-Aldrich) or an equivalent volume of saline was administered orally and by gavage to rats every morning (between 8 a.m. and 10 a.m.) for two months (8 weeks) (30). After completing the training protocol, all samples were anesthetized and sacrificed using chloroform under completely similar conditions and under baseline conditions (48 h after the last training session and 12-14 h of fasting). Immediately after isolation and washing with saline, hippocampal tissue was immediately placed in tubes containing RNA later to prevent RNA degradation, transferred to liquid nitrogen, and then stored in a refrigerator at -80 °C until measurement. Finally, Shapiro-Wilk tests were used to examine the normality of data distribution, and one-way analysis of variance and Tukey's post hoc test were used using SPSS statistical software (version 26). A P-value ≤ 0.05 was considered statistically significant.

RESULTS

Data analysis revealed a significant difference in the rate of changes in γ-secretase gene expression in hippocampal tissue between different groups (p=0.0001, F=18.740). The results of the post hoc test showed a significant increase in the rate of changes in γ-secretase gene expression in the AD (p=0.0001), ADT (p=0.002), and ADRSV (p=0.0001) groups compared to NO. Additionally, a significant decrease was observed in the ADT (p=0.024) and ADTRSV (p=0.0001) groups compared to AD; and ADTRSV compared to the ADT (p=0.029) and ADRSV (p=0.001) groups.
In addition, a significant difference was observed in the rate of changes in β-secretase gene expression in hippocampal tissue between different groups (p=0.0001, F=16.811). The results of the post hoc test also showed a significant increase in the rate of changes in β-secretase gene expression in the AD (p=0.0001), ADT (p=0.001) and ADRSV (p=0.0001) groups compared to NO. Furthermore, a significant decrease was observed in the ADT (p=0.036) and ADTRSV (p=0.0001) groups compared to AD; and ADTRSV compared to the ADT (p=0.047) and ADRSV (p=0.021) groups.

CONCLUSION

The present study showed that induction of Alzheimer's disease with Aβ leads to increased expression of β and γ secretase enzymes in the hippocampus. Interval training significantly reduced this expression, while resveratrol alone had no significant effect. These findings suggest the potential for developing non-invasive strategies to prevent or slow the progression of Alzheimer's disease. However, clinical studies are required to confirm these effects in humans.

Ethical Considerations
Compliance with Ethical Guidelines

The present study has received the Code of Ethics No. IR.IAU.SARI.REC.1404.153 from the Faculty of Medical Sciences, Sari Branch, Islamic Azad University.

Fundings

This research received no financial support.

Authors’ Contribution

All authors of this article participated in the
design, implementation, data analysis, and writing of all parts of the research.

Conflicts of Interest

The authors declare that they have no conflicts of interest regarding the publication of this article.

Acknowledgments

The present study is based on a master's thesis in exercise physiology conducted at Islamic Azad University.
Type of Study: Research | Subject: Physiology
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