Bioinformatics and system biology approach to identify influences of BDNF on depression model

摘要

OBJECTIVE The classic animal model of depression is CUMS,and one of the hypotheses is related to the decrease of brain-de⁃rived neurotrophic factor(BNDF)expression in the brain,and its corresponding animal model is BDNF knockdown mice.BDNF can promote neu⁃ronal differentiation,maintain neuronal growth,and repair neuronal damage.The reduction of BDNF is related to the severity of depression.In contrast,the deletion of IDO-1 could promote the maintain the homeostasis of neurotransmitters in the brain.Therefore,the construction of BDNF and IDO-1 models for sequencing comparison can reveal the neurotransmitter hypothesis of de⁃pression from the transcriptome level.METH⁃ODS In order to obtain its transcriptome expres⁃sion profile,firstly construct BDNF knockdown,IDO-1 knockout and CUMS model.The differen⁃tial expression of mRNAs was done by sequenc⁃ing provider BGI,conducting R for analyze.Clus⁃terproflier was used to enrich GO and KEGG pathway annotations.The ceRNA package was used search database LncRNA2Target to dig potential lncRNAs.Finally,the Stringdb was used to construct the PPI network.RESULTS We identified a large number of mRNAs in mice normal and depression-like tissues from diverse genomic locations,and these mRNAs were col⁃lected from medial prefrontal cortex(mPFC)manner.Based on the analysis of the enrichment pathway and ceRNA network,we found numer⁃ous abundant mRNAs are specifically expressed in gene editing group,and differentially expressed in depression-like compared with normal tissues or depression-like antagonism group.Indicates that they serve a specific function in specific pathways.We focused on the mPFC sequencing of gene modification mice especially in BDNF+/-and IDO-/-.There is a relatively large difference in expression matrix.Certain mRNA,like Ptbp1,are predominantly expressed in comparison of BDNF+/-and other groups,and present at sub⁃stantial levels,that suggest these mRNAs are purposefully produced.Furtherly analysis of cor⁃relation map,Ptbp1 are related to the protection of vulnerable neuronal circuits and pathways are clustered in nervous system development and synapse organization.CONCLUSION We described the potential enrichment DEGs and its pathway in three model mice related to depres⁃sion.We propose gene regulation by the ceRNA network in the progression of depression mod⁃els,which could help in revealing the new mech⁃anisms and understranding of neurotransmitter hypothesis of depression.