| Objectives: Posttraumatic Stress Disorder(PTSD),also known as delayed psychogenic reaction,refers to the delay and long-term individual delay caused by sudden,threatening or catastrophic life events(such as earthquakes,tsunamis,floods,etc.)Existing mental disorders.At present there is no specific treatment for PTSD,and selective serotonin reuptake inhibitors(SSRIs)are currently the drug of choice.Clinical studies have found abnormalities in the amygdala and hippocampus in patients with PTSD.When the body is stressed,the homeostasis is unbalanced.The hippocampus plays an important role in the learning and memory formation of new things.The amygdala participates in the emotion control,and apoptosis occurs in the hippocampus and amygdala neurons.Fluoxetine can significantly improve the behavioral symptoms of PTSD patients and rats,but its specific mechanism of action remains unclear.In this study,we use the rat PTSD model,through the following three aspects of fluoxetine on PTSD hippocampus and The mechanism of action of amygdala,1)Serotonergic receptors: 5-HT1 AR and 5-HT2 AR expression changes;2)changes in the expression of synaptophysin PSD-95 and Synapsin I;3)the changes of PERK pathway.It is hoped that the solution of these problems can provide a reliable experimental basis for clinical fluoxetine in the treatment of PTSD.Methods: Single-Prolonged Stress(PTSD-SPS)was used to construct animal model of PTSD.Behavioral methods were used to detect behavioral changes in rats.Morphology methods included the Morris Water Maze Test(MWM),the Plus Maze Test and the Open Field Maze Test.Morris water maze was used to detect the spatial learning and memory abilities of rats in each group.Plus Maze Test and Open Field Maze Test were used to detect the changes of anxiety in each group.The immunostaining of PSD-95,Synapsin I,5-HT1 AR,5-HT2 AR,PERK,P-PERK,P-e IF2?,ATF4,CHOP,Caspase 3 and Capase 12 in hippocampus and amygdala neurons of rats was detected by Western blotting Reactivity.At the same time,Real-time PCR was used to detect the m RNA expression of PERK,P-PERK,P-e IF2?,ATF4 and CHOP in hippocampus and amygdala.Results:1.Behavioral test found that SPS decreased spatial memory ability and increased anxiety levels,which were significantly improved after fluoxetine administration.2.Western blotting detected that the levels of PSD-95 and Synapsin I in the hippocampal neurons of SPS rats were decreased,while the expression of the two proteins was increased in the amygdala.Fluoxetine administration can reverse these changes in the two areas.3.Western blotting detected that the expression of 5-HT1 A decreased in hippocampus but increased in amygdala in SPS rats,while the expression of 5-HT2 A in both hippocampus and amygdala was increased.However,these changes were also normalized by fluoxetine administration.4.The results of western blotting detecting showed that both PERK pathway protein and apoptosis factor induced by SPS were increased in hippocampus and amygdala,while fluoxetine also corrected the changes of PERK pathway and apoptosis factors induced by SPS in both brain regions.Real-time PCR was used to detect m RNA expression of PERK pathway in the hippocampus and amygdala of SPS rats,while fluoxetine also inhibited PERK pathway m RNA expression in these two regions.Conclusion:1.SPS caused spatial memory impairment and serious anxiety in rats,and fluoxetine could correct behavioral changes induced by SPS.2.luoxetine may be effective in correcting changed synaptic proteins and enhanced apoptosis in the hippocampus and amygdala caused by SPS. |
PDF Full Text Request