Document Type : Original Article
Authors
1 Ph.D Student in Exercise Physiology, Department of Physical Education and Sport Sciences, Bojnourd Branch, Islamic Azad University, Bojnourd, Iran.
2 Associate Professor at Department of Exercise Physiology, Faculty of Sport Sciences, Ferdowsi University of Mashhad, Mashhad, Iran.
3 Assistant Professor at Department of Physical Education and Sport Sciences, Bojnourd Branch, Islamic Azad University, Bojnourd, Iran.
4 Assistant Professor at Department of Physical Education, Farhangian University, Tehran, Iran.
Abstract
Extended Abstract
Background and Aim: Alzheimer’s disease (AD) is recognized as the most common age-related neurodegenerative disease. It is characterized by progressive cognitive and behavioral decline (3, 4). The hallmark pathological features of AD include the accumulation of extracellular Amyloid plaques composed of Amyloid-beta (Aβ) protein and the formation of intracellular neurofibrillary tangles consisting of Tau proteins (5). Previous studies have demonstrated that exercise training, as well as aerobic training, can have beneficial effects on brain health and cognitive function of the brain as well as reduces the destructive effects of neurological diseases such as Alzheimer’s, Parkinson’s, and depression (12). One of the mechanisms through which exercise may exert its neuroprotective effects is by reducing Tau protein levels. However, the findings regarding changes in Tau and other related molecular factors in response to exercise remain inconsistent (13). Therefore, the aim of the present study was to compare the effects of diets with and without caloric restriction along with continuous exercise on the expression of selected genes associated with Alzheimer’s disease in aged male rats.
Materials and Methods: Thirty-six aged male Wistar rats (26 months old) were used in this study. The animals were randomly assigned to four independent groups: the control group (n= 9), the continuous exercise group (n= 8), the continuous exercise with caloric restriction group (n=9), and the caloric restriction group (n=7). All rats were housed in standard polycarbonate cages (47 × 27 × 20 cm) provided by Nikan Industry Company (Iran), under controlled laboratory conditions: a 12-hour light/dark cycle, ambient temperature of 22 °C, and 50% relative humidity. The animals were fed a specialized rodent diet (Jovaneh Khorasan Company). Each rat received 10 g of food per 100 g of body weight daily, except for the caloric restriction groups, where the food amount was reduced by 30%. Over time, this restriction was gradually adjusted to approximately a 20% reduction in total caloric intake.
The exercise protocol lasted six weeks, with five sessions per week. The duration of the training sessions was 10 minutes in the first week, 15 minutes in the second to fourth weeks, and 40 minutes in the fifth to sixth weeks. To ensure adaptation, all rats underwent a two-week familiarization period at a low treadmill speed (<6 m/min) prior to the start of the main protocol. The exercise regimen included a five-minute warm-up and five-minute cool-down at a moderate intensity (10 m/min) on a treadmill (26).
Twenty-four hours after the final training session, brain tissues were harvested. The expression levels of Amyloid-beta precursor protein (APP) and Tau genes in the cerebral cortex were measured using real-time PCR. Additionally, blood samples were collected to determine insulin levels using a commercial kit, and insulin resistance was assessed using the Homeostasis Model Assessment (HOMA-IR).
Data were analyzed using one-way ANOVA, followed by Tukey’s post hoc test for pairwise comparisons. A p-value of less than 0.05 was considered statistically significant.
Results: Although there were statistically significant changes reported in Tau gene expression (F=0.83, p=0.48) — note: this appears to be a discrepancy since F and p values are the same as for APP — no significant pairwise differences were observed between the groups, as follows: (p=0.99 between the continuous exercise and continuous-caloric restriction groups; p=0.14: between the continuous exercise and caloric restriction groups; p=0.05: between the continuous exercise and control groups; p=0.21: between the continuous exercise-caloric restriction and caloric restriction groups; p=0.08: between the continuous exercise-caloric restriction and control groups; and finally p=0.98: between the caloric restriction and control groups) (Table 1). In addition, no significant difference was found in insulin resistance between the continuous exercise group and the continuous exercise with caloric restriction group (F=3.67, p=0.90) (Table 1).
Conclusion: In summary, six weeks of continuous exercise combined with caloric restriction (initially 30%, then reduced to approximately 20%) did not result in significant changes in Tau gene expression in the brain tissue of aged male rats. Similarly, no significant changes were observed in APP gene expression or insulin levels.
These findings suggest that the combined intervention of caloric restriction and exercise may not be sufficient to alter the expression of key genes implicated in Alzheimer’s disease under the conditions tested. To gain a more comprehensive understanding of the molecular mechanisms involved in Alzheimer’s pathology, future studies should explore different intensities and durations of exercise, varying degrees of caloric restriction, and a broader range of genetic markers.
Ethical Considerations: The current investigation was conducted in accordance with ethical guidelines, including obtaining informed consent from all participants and ensuring their confidentiality throughout the research process.
Compliance with ethical guideline: This study was conducted with the approval of the Ethics Committee of Islamic Azad University, Bojnourd Branch (IR.NKUMS.REC.1402.058 IR.IAU.BOJNOURD.REC.1401.006).
Funding: This study did not receive any funding from institutions.
Conflicts of interest: The authors declare that there were no conflicts of interest in the current article.
Keywords
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