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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1472468

Identification and experimental validation of hub genes underlying depressive-like behaviors induced by chronic social defeat stress

Provisionally accepted
Yexiang Chen Yexiang Chen *Yunhao Jiang Yunhao Jiang Xingcong Jiang Xingcong Jiang Caiyu Zhai Caiyu Zhai Yifei Wang Yifei Wang *Chi Xu Chi Xu *
  • Zhejiang Chinese Medical University, Hangzhou, China

The final, formatted version of the article will be published soon.

    Major depressive disorder (MDD), marked by severe neuropsychiatric conditions and profound cognitive deficits, continues to pose both etiological and therapeutic challenges. Through transcriptomic profiling, biomarkers associated with MDD have been identified, enabling the prediction of clinical outcomes. This research sought to identify key diagnostic genes and explore their potential role in MDD. The Gene Expression Omnibus (GEO) repository was leveraged to obtain gene expression data related to MDD. Differentially expressed genes (DEGs) were discovered and analyzed for enrichment using Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Subsequently, the associated gene modules were analyzed through integrated weighted gene co-expression network analysis. The analysis revealed three key genes, namely AGA, FBXO38, and RGS5, through the application of the Least Absolute Shrinkage and Selection Operator (LASSO) approach, the Random Forest (RF) algorithm, and the Support Vector Machine with Recursive Feature Elimination (SVM-RFE) technique. Chronic social defeat stress (CSDS), which could effectively emulate depressive-like behavior was employed for depressive-like behavior model construction. AGA, FBXO38, and RGS5 genes in the dorsolateral prefrontal cortex (dlPFC) were detected by qPCR and Western bolt after CSDS, and the results were consistent with the analyses from the datasets (GSE53987 and GSE54568). Based on our research, AGA, FBXO38, and RGS5 are potential biomarkers for MDD, and these key genes could be advantageous for MDD risk prediction.

    Keywords: Major depressive disorder (MDD), Differentially Expressed Genes (DEGs), Aspartylglucosaminidase (AGA), F-box protein 38 (FBXO38), Regulator of G protein signaling 5 (RGS5), Chronic social defeat stress (CSDS)

    Received: 29 Jul 2024; Accepted: 23 Sep 2024.

    Copyright: © 2024 Chen, Jiang, Jiang, Zhai, Wang and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yexiang Chen, Zhejiang Chinese Medical University, Hangzhou, China
    Yifei Wang, Zhejiang Chinese Medical University, Hangzhou, China
    Chi Xu, Zhejiang Chinese Medical University, Hangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.