Abstract
Post-traumatic stress disorder (PTSD) is a stress-related condition that can be triggered by witnessing or experiencing a life-threatening event, such as a war, natural disaster, terrorist attack, major accident, or assault. PTSD is caused by dysfunction of the hippocampus and causes problems associated with brain functioning, such as anxiety, depression, and cognitive impairment. Exercise is known to have a positive effect on brain function, especially in the hippocampus. In this study, we investigated the effect of aerobic exercise on mitochondrial function and neuroplasticity in the hippocampus as well as behavioral changes in animal models of PTSD. Exposure to severe stress resulted in mitochondrial dysfunction in the hippocampus, including impaired Ca2+ homeostasis, an increase in reactive oxygen species such as H2O2, a decrease in the O2 respiration rate, and overexpression of membrane permeability transition pore-related proteins, including voltage-dependent anion channel, adenine nucleotide translocase, and cyclophilin-D. Exposure to extreme stress also decreased neuroplasticity by increasing apoptosis and decreasing the brain-derived neurotrophic factor level and neurogenesis, resulting in increased anxiety, depression, and cognitive impairment. The impairments in mitochondrial function and neuroplasticity in the hippocampus, as well as anxiety, depression, and cognitive impairment, were all improved by exercise. Exercise-induced improvement of the brain-derived neurotrophic factor level in particular might alter mitochondrial function, neuroplasticity, and the rate of apoptosis in the hippocampus. Therefore, exercise might be an important non-pharmacological intervention for the prevention and treatment of the pathobiology of PTSD.