| Background:Post-traumatic stress disorder (PTSD) is a kind of mental disease which caused by life-threatening events, such as major accident, natural disaster and military action. Main clusters of symptoms of PTSD could be summarized as flashbacks of traumatic event; increased arousal symptoms; avoid things, people, or situation associated with traumatic incident. Previous studies indicated that the dysfunction of 5-HT system plays a crucial role in the pathology of PTSD, and the disruption of 5-HT receptors caused by stress during development could be a key factor of the formation of individual’anxious phenotype. Recent literatures have pointed out miRNA-135a in prefrontal cortex (PFC) and miRNA-16 in hippocampus (HIP) involving in anxiety and depression-like behaviors via regulate the 5-HT system. But the role of early-life stress, the 5-HT receptors and specific microRNAs in the pathogenesis of PTSD has not clarified yet. The study observed the influences of early life traumatic stress on the expression of 5-HT receptors and specific microRNAs in rats’prefrontal cortex and hippocampus.Objectives:1. The aim of the study is to observe the changes of depressive and anxiety like behaviors,5-HT receptors expression in PFC and HIP in adult rats which experienced adolescent traumatic stress; and the effects of progressive treadmill exercise on the depressive and anxiety like behaviors of rats; and also 5-HT receptors expression after exercise.2. To observe the dynamic changes of depressive and anxiety like behaviors, the cognitive function,5-HT receptors expression, miRNA-135a in PFC and miRNA-16 in HIP in both adolescent rats and adult rats; and the effects of paroxetine hydrochloride and CRF1 receptor antagonist (CP-154.526) on the depressive and anxiety like behaviors of rats; and also 5-HT receptors expression in PFC and HIP; miRNA-135a expression in PFC and miRNA-16 expression in HIP.Methods:1.33 healthy Wistar rats (male,21 days old) were randomly distributed into three groups (n=l 1 per group):the control group, the PTSD group, the exercise group. The PTSD animal model was established by inescapable electric foot shock stress (6 days). The behavioral changes were assessed by the elevated plus maze (EPM) test and the open field (OF) test. Immunohistochemistry test and Western Blotting test were used to calculate the expression of 5-HT receptors in PFC and HIP. 2.80 healthy Wistar rats (male,21 days old) were randomly assigned into 8 groups (n=10 per group):the adolescent control group, the adolescent PTSD group, the adolescent PTSD and anti-depression group, the adolescent PTSD and CRF antagonist group, the adulthood control group, the adulthood PTSD group, the adulthood PTSD and anti-depression group, the adulthood PTSD and CRF antagonist group. All PTSD rats received PTSD model protocol in adolescent stage (6 days). Anti-depressants (paroxetine hydrochloride) and CRF1 receptor antagonist (CP-154, 526) were taken as intervention means. The EPM test, OF test, novelty suppressed feeding (NSF) test and morris water maze (MWM) test were used to estimate behavioral changes. Immunohistochemistry test and Western Blotting test were used to detect the expression of 5-HT1AR in PFC and HIP, the alteration of miRNA-135a in PFC and miRNA-16 in HIP was detected by RT-qPCR.Results:1. Compared with control group, PTSD rats showed anxiety and depression-like behaviors and a significant enhancing expression of 5-HT1AR in PFC,5-HT2CR in PFC and HIP; while regular treadmill exercise improved anxiety and depression-like behaviors, decreased the 5-HT1AR expression in PFC,5-HT2CR in PFC and HIP in exercise group.2. AdoP rats displayed reduced miRNA-135a and increased 5-HT1AR in PFC, and these changes continued to their adulthood. Rats in AdoP group expressed excessive miRNA-16 in HIP (without significant 5-HT1AR change) and the change lasted for a long time. Paroxetine hydrochloride and CP-154,526 improved the negative symptoms and changes which induced by early life stress experience.Conclusion:1. Early-life traumatic stress resulted in a persisted anxiety and depression-like behaviors in both adolescence and adult rats; led to dysfunctions of 5-HT1AR in PFC and 5-HT2CR in both PFC and HIP.2. Early-life traumatic stress induced anxiety and depression-like behaviors; and the alternation of miRNA-135a in PFC and miRNA-16 in HIP, which indicates miRNA-135a in PFC and miRNA-16 in HIP play important roles in the pathology of PTSD.3. The regular treadmill exercise, anti-depressant (paroxetine hydrochloride) and CRF1 receptor antagonist (CP-154, 526) can alleviate PTSD symptoms of rats; reverse the changes of 5-HT receptors expression. |
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