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. 2019 Feb 27:10:302.
doi: 10.3389/fpsyg.2019.00302. eCollection 2019.

Identification of Key Genes and Pathways in Post-traumatic Stress Disorder Using Microarray Analysis

Yaoyao Bian  1 , Lili Yang  2   3 , Min Zhao  2 , Zhengjun Li  4 , Yuying Xu  1 , Guilian Zhou  1 , Wenlin Li  3 , Li Zeng  2   3
Affiliations

Identification of Key Genes and Pathways in Post-traumatic Stress Disorder Using Microarray Analysis

Yaoyao Bian et al. Front Psychol. .

Abstract

Introduction: Post-traumatic stress disorder (PTSD) is characterized by impaired fear extinction, excessive anxiety, and depression. However, the potential pathogenesis and cause of PTSD are not fully understood. Hence, the purpose of this study was to identify key genes and pathway involved in PTSD and reveal underlying molecular mechanisms by using bioinformatics analysis. Methods: The mRNA microarray expression profile dataset was retrieved and downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened using GEO2R. Gene ontology (GO) was used for gene function annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was performed for enrichment analysis. Subsequently, protein-protein interaction (PPI) network and module analysis by the plugin MCODE were mapped by Cytoscape software. Finally, these key genes were verified in stress-exposed models by Real-Time quantitative (qRT-PCR). In addition, we performed text mining among the key genes and pathway with PTSD by using COREMINE. Results: A total of 1004 DEGs were identified. Gene functional annotations and enrichment analysis indicated that the most associated pathway was closely related to the Wnt signaling pathway. Using PPI network and module analysis, we identified a group of "seed" genes. These genes were further verified by qRT-PCR. In addition, text mining indicated that the altered CYP1A2, SYT1, and NLGN1 affecting PTSD might work via the Wnt signaling pathway. Conclusion: By using bioinformatics analysis, we identified a number of genes and relevant pathway which may represent key mechanisms associated with PTSD. However, these findings require verification in future experimental studies.

Keywords: PTSD; bioinformatics analysis; key genes; key pathways; microarray analysis.

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Figures

FIGURE 1
FIGURE 1
(A) Cage-within-cage configuration for aggressor exposure. (B) The protocol timeline of single-housed home cage (10 consecutive days with aggressor exposure and 6 weeks rest).
FIGURE 2
FIGURE 2
Volcano plot of differential expression genes. Red points as up-regulated genes, green plots as down-regulated genes, and black plots as genes with no significant difference.
FIGURE 3
FIGURE 3
The differential expressed protein–protein interaction network. Proteins were represented with color nodes, and interactions were presented with edges.
FIGURE 4
FIGURE 4
Relative expression level of the “seed” genes in hippocampus region in response to stress exposure. The expression level of mRNAs was conducted using qRT-PCR. Results were shown as mean ± SD, ∗P < 0.05.
FIGURE 5
FIGURE 5
The linear relationship among the “seed” genes, and the Wnt signaling pathway with PTSD by using COREMINE. Three “seed” genes were associated with the Wnt signaling pathway and PTSD. The thicker the line, the closer the connection between the two ends.
FIGURE 6
FIGURE 6
FST and TST immobility time in animal testing and path length of OFT. Results were shown as mean ± SD, ∗P < 0.05.
See this image and copyright information in PMC

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