Molecular mechanism of reward treatment ameliorating chronic stress-induced depressive-like behavior assessed by sequencing miRNA and mRNA in medial prefrontal cortex

Tingting An,Zhenhua Song,Jin-Hui Wang

doi:10.1016/j.bbrc.2020.05.158

Tingting An, Zhenhua Song + Show 1 more

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https://doi.org/10.1016/j.bbrc.2020.05.158

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Abstract

Chronic stress and lack of reward may reduce the function of the brain’s reward circuits, leading to major depressive disorder. The effect of reward treatment on chronic stress-induced depression-like behaviors and its molecular mechanism in the brain remain unclear. In this study, companion communication was used as a reward to study the effect of reward on CUMS-induced depression-like behaviors, and mRNA and miRNA profiles in the medial prefrontal cortex harvested from mice with depression-like and resilient behaviors were established by high-throughput sequencing. The results showed that accompanying with companion ameliorated CUMS-induced depression-like behaviors in mice. Furthermore, 45 differentially expressed genes (DEGs) associated with depression-like behaviors, 8 DEGs associated with resilience and 59 DEGs associated with nature reward (companion) were identified, and 196 differentially expressed miRNAs were found to be associated with companion. Based on the differentially expressed miRNAs and DEGs data, miRNA-mRNA network was established to be associated with companion. Taken together, our data here provided a method to ameliorate depression-like behaviors, and numerous potential drug targets for the prevention or treatment of depression.

Highlights

Major depressive disorder (MDD) is a disease that seriously endangers human health and mental state
The results provided evidence that accompanying with companion ameliorated chronic unpredictable mild stress (CUMS)-induced depression-like behaviors in mice. 45 differentially expressed genes (DEGs) are associated with depression-like behaviors, 8 DEGs are associated with resilience and 59 DEGs are associated with nature reward were identified
Studies on major depressive disorder have showed that lack of rewards in life can cause the brain's reward circuits to be not sufficiently activated or actively used, and may reduce the function of the brain's reward circuits [7, 8], including ventral tegmental area (VTA), nucleus accumbens (NAc) and prefrontal cortex (PFC), which may lead to major depressive disorder [9,10,11]

Summary

Introduction

Major depressive disorder (MDD) is a disease that seriously endangers human health and mental state. Chronic stress and lack of reward may reduce the function of the brain's reward circuits, leading to major depressive disorder. Rewards can be divided into natural rewards and drug rewards The former refers to innate desire or dependence on certain things, such as food, sounds, smells, food, sex, and social interactions [16, 17]. Studies have shown that music has an important role in emotional arousal and hedonic regulation [21,22,23] and music intervention can improve the symptoms of MDD, including sleep quality, quality of life, and lack of pleasure [24,25,26]. Increased attention to reward processing within the therapeutic process may improve clinical outcomes [29]

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