Anxiolytic-Like Effects Of Treadmill Exercise On Post-Traumatic Stress Disorder And Their Mechanism

Post-traumatic stress disorder(PTSD)is a disabling anxiety disorder that occurs when someone is exposure to catastrophic and threatening events,such as: natural disasters,wartime situations,traffic accidents and/or terrorist attacks.Research based evidence supports the beneficial effects of regular physical exercise on physical health,cognitive deficits and mood disorders such as anxiety and depression.This study aimed to investigate whether or not treadmill exercise has therapeutic effects in two Post-traumatic stress disorder(PTSD)models,and to explore the underlying mechanisms on one of the PTSD models.A time-dependent sensitization(TDS)model and a fear conditioning(FC)model were developed to evaluate the anti-PTSD-like effects of moderate treadmill exercise with 4/5-week running programm.This study explored the relationship between anti-inflammatory effects of exercise on PTSD rats.High-performance liquid chromatography(HPLC)technology was used to determine the levels of monoamine neurotransmitters in the hippocampus and prefrontal cortex in TDS rats.The western blot method was used to assay key proteins expression in BDNF/PI3K/Akt/CREB signaling pathway.Our results showed that(1)the TDS and FC procedures induced several behavioral deficiencies,such as an increase in the freezing time(P<0.001)and a decrease in the percentage of entries into the open arms and time spent in the open arms(P<0.05),and that these deficiencies were reversed by treadmill exercise(P<0.05).(3)Further monoamine assays revealed that the treadmill exercise significantly increased serotonin(5-HT)levels(P<0.05)in the hippocampus and decreased dopamine(DA)levels(P<0.05)in the prefrontal cortex.(4)Elisa test showed that TDS rat significantly decreased the level of TNF-α(P<0.05)compared with CON.Exercise significantly increased the level of TNF-α(P<0.05).(5)Western blotting data demonstrated that exercise normalized the decreased BDNF/TrkB/pAkt/pCREB levels(P<0.05、P<0.01)in the hippocampus in TDS rats compared with TDS.The present study demonstrated that treadmill exercise ameliorated contextual fear conditioning and anxiety-like behavior in two rat PTSD models.Mechanism studies indicated that increased 5-HT levels in the hippocampus decreased DA levels in the prefrontal cortex and increased TNF-α levels,as well as upregulation of BDNF and the related PI3K/AKT/CREB signaling pathway,may be involved in the therapeutic effects of treadmill exercise on alleviating the PTSD.