<p>Identification of key genes, pathways and miRNA/mRNA regulatory networks of CUMS-induced depression in nucleus accumbens by integrated bioinformatics analysis</p>

Abstract

Introduction: Major depressive disorder (MDD) is a recurrent, devastating mental disorder, which affects .350 million people worldwide, and exerts substantial public health and financial costs to society. Thus, there is a significant need to discover innovative therapeutics to treat depression efficiently. Stress-induced dysfunction in the subtype of neuronal cells and the change of synaptic plasticity and structural plasticity of nucleus accumbens (NAc) are implicated in depression symptomology. However, the molecular and epigenetic mechanisms and stresses to the NAc pathological changes in depression remain elusive. Materials and methods: In this study, treatment group mice were treated continually with the chronic unpredictable mild stress (CUMS) until expression of depression-like behaviors were found. Depression was confirmed with sucrose preference, novelty-suppressed feeding, forced swimming, and tail suspension tests. We applied high-throughput RNA sequencing to assess microRNA expression and transcriptional profiles in the NAc tissue from depression-like behaviors mice and control mice. The regulatory network of miRNAs/mRNAs was constructed based on the high-throughput RNA sequence and bioinformatics software predictions. Results: A total of 17 miRNAs and 10 mRNAs were significantly upregulated in the NAc of CUMS-induced mice with depression-like behaviors, and 12 miRNAs and 29 mRNAs were downregulated. A series of bioinformatics analyses showed that these altered miRNAs predicted target mRNA and differentially expressed mRNAs were significantly enriched in the MAPK signaling pathway, GABAergic synapse, dopaminergic synapse, cytokine-cytokine receptor interaction, axon guidance, regulation of autophagy, and so on. Furthermore, dual luciferase report assay and qRT-PCR results validated the miRNA/mRNA regulatory network. Conclusion: The deteriorations of GABAergic synapses, dopaminergic synapses, neurotransmitter synthesis, as well as autophagy-associated apoptotic pathway are associated with the molecular pathological mechanism of CUMS-induced depression.

WITHDRAWN: Identification of Non-coding RNA&nbsp;Biomarkers in Stress-induced Depression via Comprehensive Analysis of Competing Endogenous RNA&nbsp;Network

“…6. There were evidences that miR-338-3p and pvalb were identi ed to be unnormal expressed in depression, suggesting play a key role pathogenesis of depression [47,48]. MiR-338-3p is a mature miRNA.…”

Antidepressant mechanism of classical herbal formula lily bulb and Rehmannia decoction: insights from gene expression profile of medial prefrontal cortex of mice with stress‐induced depression‐like behavior

“…The protocol for RNA isolation and sequencing was reported in our published study . In brief, after depression‐like behavior tests, mice were anesthetized using isoflurane and rapidly sacrificed by decollation.…”

<p>Chronic Stress in a Rat Model of Depression Disturbs the Glutamine–Glutamate–GABA Cycle in the Striatum, Hippocampus, and Cerebellum</p>

“…9,10 A transcriptome study of the striatum suggested that dysfunction of dopaminergic synapses, GABAergic synapses, and neurotransmitter synthesis is involved in the pathogenesis of chronic unpredictable mild stress (CUMS)-induced depression. 11 It has also been reported that the use of deep brain stimulation in the striatum could reduce 50% of depression symptoms in patients with refractory depression. 12 In addition, depression severity and the antidepressant effects of ketamine have been shown to depend on the structure and function of the striatum.…”