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BMC Medical Informatics and Decision Making
Published in: BMC Medical Informatics and Decision Making 6/2019

Open Access 01-12-2019 | Antidepressant Drugs | Research

Expression alteration of microRNAs in Nucleus Accumbens is associated with chronic stress and antidepressant treatment in rats

Authors: Weichen Song, Yifeng Shen, Yanhua Zhang, Sufang Peng, Ran Zhang, Ailing Ning, Huafang Li, Xia Li, Guan Ning Lin, Shunying Yu

Published in: BMC Medical Informatics and Decision Making | Special Issue 6/2019

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Abstract

Background

Nucleus Accumbens (NAc) is a vital brain region for the process of reward and stress, whereas microRNA plays a crucial role in depression pathology. However, the abnormality of NAc miRNA expression during the stress-induced depression and antidepressant treatment, as well as its biological significance, are still unknown.

Methods

We performed the small RNA-sequencing in NAc of rats from three groups: control, chronic unpredictable mild stress (CUMS), and CUMS with an antidepressant, Escitalopram. We applied an integrative pipeline for analyzing the miRNA expression alternation in different model groups, including differential expression analysis, co-expression analysis, as well as a subsequent pathway/network analysis to discover both miRNA alteration pattern and its biological significance.

Result

A total of 423 miRNAs were included in analysis.18/8 differential expressing (DE) miRNA (adjusted p < 0.05, |log2FC| > 1) were observed in controls Vs. depression/depression Vs. treatment, 2 of which are overlapping. 78% (14/18) of these miRNAs showed opposite trends of alteration in stress and treatment. Two micro RNA, miR-10b-5p and miR-214-3p, appeared to be hubs in the regulation networks and also among the top findings in both differential analyses. Using co-expression analysis, we found a functional module that strongly correlated with stress (R = 0.96, P = 0.003), and another functional module with a moderate correlation with anhedonia (R = 0.89, P = 0.02). We also found that predicted targets of these miRNAs were significantly enriched in the Ras signaling pathway, which is associated with both depression, anhedonia, and antidepressant treatment.

Conclusion

Escitalopram treatment can significantly reverse NAc miRNA abnormality induced by chronic stress. However, the novel miRNA alteration that is absent in stress pathology also emerges, which means that antidepressant treatment is unlikely to bring miRNA expression back to the same level as the controls. Also, the Ras-signaling pathway may be involved in explaining the depression disease etiology, the clinical symptom, and treatment response of stress-induced depression.
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Metadata
Title
Expression alteration of microRNAs in Nucleus Accumbens is associated with chronic stress and antidepressant treatment in rats
Authors
Weichen Song
Yifeng Shen
Yanhua Zhang
Sufang Peng
Ran Zhang
Ailing Ning
Huafang Li
Xia Li
Guan Ning Lin
Shunying Yu
Publication date
01-12-2019
Publisher
BioMed Central
DOI
https://doi.org/10.1186/s12911-019-0964-z

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