Physical Exercise Inhibits Cognitive Impairment and Memory Loss in Aged Mice, and Enhances Pre- and Post-Synaptic Proteins in the Hippocampus of Young and Aged Mice
A scientific paper authored by Ricardo Augusto Leoni de Sousa and his research team was published in Volume 26, Issue 31 of the journal “Neuromolecular Medicine” in 2024. The paper is titled “Physical exercise inhibits cognitive impairment and memory loss in aged mice, and enhances pre- and post-synaptic proteins in the hippocampus of young and aged mice”. This study aimed to evaluate the effects of physical exercise, particularly swimming, on the brains and behavior of young and aged mice. In this news report, we will provide a detailed introduction to the background, research methods, experimental results, and conclusions of this study.
Research Background
As bioenergetic challenges arise (such as sustained activity in neural circuits and stress from physical exercise), brain cells typically adapt. These adaptive responses involve the generation of new synapses, “strengthening” of existing synapses, and the production of new neurons. Modern research indicates that bioenergetic challenges (such as Alzheimer’s disease and aging) activate transcription factors at the molecular level, involving various metabolic, oxidative, excitotoxic, and proteotoxic stresses, all of which are related to the pathogenesis of various brain diseases. On the other hand, physical exercise, as an intermittent bioenergetic challenge, can delay aging-related factors. This study was based on this background to explore the effects of physical exercise on the brain and behavior.
Paper Source
The main authors of this paper include Ricardo Augusto Leoni de Sousa and others, who are from institutions such as the Brazilian Federal Department of Education, the Brazilian Society of Physiological Sciences, and the Neuroscience and Exercise Research Group. The paper was received on June 1, 2024, accepted on July 7, 2024, and published in the 2024 issue of “Neuromolecular Medicine”.
Research Methods
Experimental Design
The experimental subjects were 48 male C57BL/6J mice, divided into 4 groups (12 mice per group): 3-month sedentary group (3 months-sed), 18-month sedentary group (18 months-sed), 3-month exercise group (3 months-exe), and 18-month exercise group (18 months-exe). The exercise groups underwent swimming training for 30 minutes a day, 5 days a week, for 4 weeks. Swimming training began after an adaptation week, during which swimming time gradually increased from 10 minutes to 30 minutes per day.
Behavioral Tasks
24 hours after the last swimming session, a series of behavioral tasks were conducted to assess the mice’s motor activity, anxiety performance, working memory, and spatial memory. These tasks included:
- Open Field Test (OFT): Assessing motor activity and anxiety behavior of mice by measuring their activity in an arena with central and peripheral areas.
- Novel Object Recognition (NOR) Task: Evaluating working memory of mice by testing their exploration time in an arena with identical and different objects.
- Displaced Object Recognition (DOR) Task: Different from NOR, this task tests spatial memory of mice by moving the position of an object in the arena.
The experimental tasks were recorded using the Noldus Etho Vision XT video tracking system.
Molecular and Biochemical Analysis
After completing the behavioral tasks, the mice were euthanized and their hippocampal regions were extracted for protein analysis and measurement of lipid peroxidation and redox state parameters. Protein levels were determined by Western Blot method, using BCA protein quantification kit for protein concentration determination. Lipid peroxidation was measured by thiobarbituric acid reactive substances, and redox state was determined by ferric reducing antioxidant power (FRAP) assay.
Statistical Analysis
Experimental data were analyzed using GraphPad Prism, employing one-way analysis of variance (ANOVA) with Tukey’s post-hoc test for multiple comparisons.
Research Results
Working Memory and Spatial Memory Affected by Aging
The experiment found that aged mice without physical exercise (18 months-sed group) showed cognitive decline and memory loss in working memory and spatial memory tasks. This indicates that aging leads to a decline in cognitive function.
Enhancement of Pre- and Post-synaptic Proteins
The levels of pre-synaptic protein (synaptophysin) and post-synaptic protein (PSD95) were significantly enhanced in the exercise groups (3 months-exe and 18 months-exe), while no significant changes were observed in the sedentary groups. This suggests that physical exercise can effectively improve synaptic-related protein levels in both young and aged mice, thereby improving memory function.
Reduction in Lipid Peroxidation
In the sedentary groups, aged mice (18 months-sed group) showed higher levels of lipid peroxidation, while the young exercise group (3 months-exe group) showed higher antioxidant capacity. These results further indicate that physical exercise can reduce oxidative stress damage caused by aging, protecting cognitive function.
Conclusion
This study clearly demonstrates that moderate aerobic physical exercise, such as swimming, can inhibit cognitive impairment and memory loss in aged mice, and enhance pre- and post-synaptic protein levels in the hippocampus of both young and aged mice. Additionally, physical exercise helps reduce lipid peroxidation and improve antioxidant capacity, thus providing protective effects on brain cells. These findings suggest that regular exercise is not only beneficial for physical health but also an effective means of protecting brain function.
Value and Significance of the Research
This study provides a new perspective on understanding the behavioral and molecular biological changes in the brain caused by aging and the effects of physical exercise. Although the study used a mouse model, these findings also suggest the potential effects of maintaining physical activity in preventing cognitive impairment in humans. In the future, further clinical studies may validate these findings, providing a theoretical foundation and scientific basis for preventing Alzheimer’s disease and other neurodegenerative diseases.