Effects of Physical Activity on Cognitive Function and Neuroplasticity in SPS Rats: Hippocampal Changes and BDNF Level

Abstract

Background and Purpose: Post-traumatic stress disorder (PTSD) is a type of psychotic illness that can occur after traumatic events such as war, childhood abuse, rape, natural disasters like earthquakes, and other unfortunate life events. These stresses can damage different brain areas, leading to behavioral changes associated with these regions. Chronic stress increases the activity of microglial cells, resulting in the loss of dendritic spines in the medial prefrontal cortex and hippocampus. Additionally, memory formation is impaired after stress exposure, leading to the inability to replace new memories with previous disturbing ones. The pathophysiology of PTSD involves changes in specific anatomical regions and circuits of the brain. Damage to the prefrontal cortex (PFC) can hinder the ability to forget inappropriate and disturbing memories. The PFC plays a crucial role in the brain's physiological response, providing the necessary functions to create calm, rational, and flexible responses. Studies have shown that acute stress weakens the prefrontal cortex. Medications for psychotic disorders have side effects, and there is a risk of relapse in some patients. Finding new treatment methods with greater benefits and minimal side effects is essential. Exercise, as an adjunctive treatment, may improve the structural and functional changes caused by stress. Materials and Methods: In this experiment, Wistar male laboratory rats and a single prolonged stress animal model were used as valid models for PTSD induction. Following a 4-week exercise intervention on a treadmill (forced exercise at moderate intensity) — the first two weeks at a speed of 10 m/min for half an hour a day and the second two weeks at a speed of 15 m/min for half an hour a day, 5 days per week — cognitive memory and fear extinction were evaluated using behavioral tests (ORMT and Extinction). The animals were then euthanized under deep anesthesia with ketamine and xylazine. The brains were removed, and the hippocampus was fixed for histological studies using the Golgi staining method. The prefrontal cortex was also frozen at -80°C for BDNF measurement. Results: The results of this study showed that rats suffering from PTSD exhibited a decrease in fear extinction (the ability to forget disturbing memories), an increase in freezing behavior, a reduction in cognitive memory, a decrease in BDNF levels in the prefrontal cortex, and a reduction in dendritic branches. The selected exercise program significantly improved behavioral deficits (cognitive memory and fear extinction) and reduced freezing behavior as a measure of fear. Additionally, BDNF levels in the prefrontal cortex increased, and a relative increase in dendritic branches in the hippocampus was observed after the exercise protocol. Conclusion: A regular 4-week course of moderate-intensity exercise can improve the structural and functional damage caused by stress in an animal model of PTSD, particularly in the hippocampus and prefrontal cortex, as well as ameliorate deficits in cognitive memory and reduce fear responses.

Keywords

• post-traumatic stress disorder
• cognitive memory
• fear extinction
• golgi staining
• brain-derived neurotrophic factor