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Neurobiological Mechanism Of Escape Deficit After Acute Stress-Research Of Expression Of BDNF And MiRNAs Regulators In Brain On A Rat Model

Posted on:2015-07-09Degree:MasterType:Thesis
Country:ChinaCandidate:L L NieFull Text:PDF
GTID:2284330431969291Subject:Applied Psychology
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BackgroundAs acute stress might result in neurological disorders like cognitive dysfunctions, it is often regarded as the cause of stress-related disorders. However, performances of individuals exhibit great differences even after they experienced the same stress. Yet, it is not been clearly understood about the molecular mechanisms which originate this specific heterogeneity until now. BDNF is considered to be a very important part of the loop in brain which is related to stress responding, and miRNAs regulates the expression of BDNF. So we think that both of them are very important in this specific heterogeneity. In this research, acute escape deficit (AED) paradigm was performed on rats to observe mechanisms underlying this heterogeneity, and to clarify the roles of BDNF and miRNAs in this mechanism.Objectives(1) Verifying whether there are some rats unsusceptible to acute stress or not.(2) Observing the relationship between BDNF and the susceptibility of rats to acute stress.(3) Observing relationship between BDNF and miRNAs which regulate BDNF, and also cognitive dysfunctions induced by acute stress in rats.Methods(1) Subjects, design and measuresThe subjects of this study are SD rats, inter-group control was adopted to check the affecting factors.6rats were picked randomly as control from30that were scored closely in escape evaluation, and the rest24endured acute unavoidable stress.6hours later after AUS, cognitive evaluation was carried out. Here we got6stress resilience rats as resilience group, and stress susceptible rats were more than resiliences, so we picked out6of them randomly as susceptible group. Expressions of BDNF and miRNAs in brain were scaled by real-time PCR.(2) Stress paradigm and cognitive function evaluationAcute unavoidable stress was performed in this research. Specifically, rats were endured80electric shocks (60V,7s, every30s) on foot when movements were restrained (in a case40×30×20cm3). Behavioral evaluation in this research was stress escape test. In this test, the number of escapes in30shocks was recorded to representative cognitive function of rat.(3)Evaluation of BDNF and miRNAs expressionsSamples of hippocampus and prefrontal cortex in both sides of the brain were got respectively and then blent equally by weight for real-time PCR to scale the expression.(4)Statistic methodsDatas were analyzed by Statistical Package for Social Sciences (SPSS16.0for Windows). One-way ANOVA was used to check significance of differences between groups at P<0.05. Datas were expressed by mean±SD.Results(1) Behavioral evaluationBefore the AUS, there were no statistically significant differences between groups in number of escapes(P>0.05).6hours After AUS, mean escape number of susceptible rats (1.330±1.030)was less than resilience(17.170±3.540)and controls(16.170±2.920)(P <0.05).(2) Expressions of BDNF in hippocampus and PFCAfter AUS, expressions of BDNF were lower in susceptible and resilience than in control in PFC(P<0.05); expression of BDNF in susceptible in hippocampus was higher than in control (P<0.05); expression of BDNF in resilience in hippocampus was lower than in control(P<0.05).(3) Expression of miRNAsPFCRt-1:susceptible(1.87±0.24)and resilience(1.76±0.23)were higher than control (0.98±0.17)(all P=0.00).RT-10a-5p:susceptible(0.51±0.16) was lower than control(0.94±0.15)(P=0.010); resilience(1.59±0.39) was higher than control(P=0.001)and susceptible(P=0.000).RT-195:susceptible(1.81±0.29) and resilience(1.54±0.44) were higher than control(0.95±0.27)(P=0.001, P=0.009respectively).RT-206:susceptible(0.36±0.10)was lower than control(1.03±0.23)(P=0.000); resilience(1.59±0.39)was higher than susceptible(P=0.000).HippocampusRt-1:susceptible(3.79±1.60)and resilience(4.26±1.42)were higher than control(1.01±0.25)(P=0.002, P=0.000respectively).RT-10a-5p:susceptible(0.14±0.05)and resilience(0.65±0.14)were lower than control(0.96±0.31)(P=0.000, P=0.019respectively).RT-195:susceptible(0.33±0.10)was lower than resilience(0.91±0.30)and control(0.94±0.20)(P=0.000, P=0.000respectively).RT-206:susceptible(2.59±0.41)was higher than control(1.04±0.31)(P=0.003), resilience(5.06±1.20)was higher than susceptible(P=0.000).Conclusions(1) Some rats do not show escape deficit after they endured AUS, and this phenomenon might be determined by the nature of rat itself.(2) Depressed BDNF expression in hippocampus takes its role in the mechanisms of stress resilience.(3) MiRNAs take roles in stress resilience, and part of the mechanism is to regulate expression of BDNF in brain.
Keywords/Search Tags:Stress resilience, Acute escape deficit, Hippocampus, BDNF, MiRNAs, Rats
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