Document Type : original article
Authors
1
Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
2
Department of Exercise Physiology, Faculty of Sports Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
3
Department of Sport Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Abstract
Abstract
Background and Objective:
Multiple sclerosis (MS) is a chronic, inflammatory, and autoimmune disease with multifactorial origins that significantly reduces patients' quality of life by impairing physical and cognitive functions. Physical activity has been shown to exert anti-inflammatory effects and neuroprotective actions, which may benefit MS patients by mitigating neural degeneration, particularly axonal damage. In the hippocampus, signaling pathways involving glycogen synthase kinase-3 beta (GSK3β), mechanistic target of rapamycin (mTOR), and caspase-3 play key roles in regulating cellular survival, apoptosis, proliferation, and metabolic homeostasis. Given the importance of these pathways, the current study aimed to investigate the effects of voluntary swimming exercise on the expression levels of GSK3β, mTOR, and caspase-3 proteins in the hippocampal tissue of male rats with cuprizone-induced MS.
Materials and Methods:
Twenty-one male Wistar rats (average age 12 weeks, 225 ± 16 g) were randomly assigned to three groups: healthy control, MS control, and MS with exercise. MS was induced by feeding a diet containing 0.5% cuprizone for 12 weeks. Disease induction was confirmed using the rotarod performance test. Following confirmation, the exercise group underwent a six-week voluntary swimming training protocol. In the first week, rats swam for 10 minutes without added weight, and the swimming duration increased by 5 minutes weekly. During weeks five and six, the duration was maintained at 30 minutes to ensure adaptation and avoid overtraining. After completion of the protocol, behavioral assessments were repeated, hippocampal tissues were extracted, and protein levels of GSK3β, mTOR, and caspase-3 were analyzed via Western blotting. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test (significance threshold set at p<0.05).
Research results:
A significant increase in GSK3β and caspase-3 protein levels was observed in the MS control group compared to the healthy group (P=0.001), indicating enhanced apoptotic signaling.So Conversely, mTOR expression was significantly reduced in MS rats (P=0.001). Importantly, after six weeks of swimming, levels of GSK3β and caspase-3 were significantly decreased (P<0.001), while mTOR expression increased significantly in the exercise group compared to MS controls (P<0.001).
Conclusion:
The results of this Research suggest that swimming exercise leads to beneficial molecular adaptations in the hippocampus of MS-affected rats. These include the suppression of apoptosis-related proteins and enhancement of pro-survival signaling, which may contribute to hippocampal cell preservation. Therefore, voluntary swimming could serve as a promising non-pharmacological intervention to support neuronal health in MS.
Keywords: GSK3β, mTOR, caspase-3, multiple sclerosis, physical activity, rat
Keywords
Main Subjects
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