Studies Of Changes In Brain Molecules In Mice With Depression-like And Stress Resilience-like Behaviors Based On Transcriptome

Objective: Depression is a common mental disease mainly characterized by low mood,lethargy,anhedonia,sleep disturbance,and other symptoms.Suicidal thoughts or behaviors may occur in severe depression,endangering human health and mental state.Long-term chronic stress can lead to depression,but some individuals show resilience when stressed.However,the molecular mechanisms in the brain underlying depression-like behaviors and resilience-like behaviors remain unclear.Methods: Firstly,mice were treated with chronic unpredictable mild stress(CUMS),and depression-like and resilience-like behavior mice were screened according to the behavioral data of the sucrose preference test(SPT),Y-maze test(YMT),and forced swimming test(FST).Secondly,m RNA expression profiles of prefrontal cortex(m PFC),Amygdala(Amygdala),nucleus accumbens(NAc),and Ventral tegmental area(VTA)were established using high-throughput sequencing technology,differentially expressed genes(DEGs)were screened,GO function and KEGG pathway analysis were performed bioinformatics analysis methods.Thirdly,DEGs were validated using quantitative RT-PCR technology.Results: Firstly,4 weeks of CUMS treatment induced behavioral differentiation in mice,and mice with depression-like behaviors and resilience-like behaviors were screened based on behavioral data.Secondly,the transcriptome of m PFC,Amygdala,NAc and VTA in mice with depression-like behaviors and resilient behaviors were established.Thirdly,compared with depression-like behavior mice,a total of 1841 differentially expressed genes were obtained in the m PFC of resilient behavior mice,of which 1026 were up-regulated and 815 were down-regulated;a total of 384 differentially expressed genes were obtained in the Amygdala,of which 214 were up-regulated and 170 were down-regulated;a total of 856 differentially expressed genes were obtained in the NAc,of which 437 were up-regulated and 419 genes were down-regulated;a total of 307 differentially expressed genes were obtained in the VTA,of which 109 were up-regulated and 198 were down-regulated.What is more,the differentially expressed genes analysis of the four brain regions showed that only Fgfr3,Slco1a4,Prodh and Gm15446 were differentially expressed in m PFC,Amygdala,NAc and VTA at the same time.Finally,the differentially expressed genes associated with myelin in the VTA brain region were validated by quantitative RT-PCR.Conclusion: CUMS treatments can induce depression-like behaviors and resilience-like behaviors in mice;there are significant molecular changes in m PFC,Amygdala,NAc and VTA between depressive-like behavior mice and resilience-like behavior mice,and these molecular changes show obvious brain region specificity;myelination-related genes are significantly differentially expressed in the VTA between depression-like behavior mice and resilience-like behavior mice.This study will help to understand the molecular mechanism of depressed behaviors and resilient behaviors,and provide some potential drug targets for the prevention and treatment of depression.