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通过对内侧前额叶皮质中 miRNA 和 mRNA 进行测序来评估奖赏处理改善慢性应激诱导的抑郁样行为的分子机制。

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

机构信息

Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao, Shandong, 266021, China.

Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao, Shandong, 266021, China.

出版信息

Biochem Biophys Res Commun. 2020 Jul 30;528(3):520-527. doi: 10.1016/j.bbrc.2020.05.158. Epub 2020 Jun 2.

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.

摘要

慢性应激和缺乏奖励可能会降低大脑奖励回路的功能,导致重度抑郁症。奖励治疗对慢性应激诱导的抑郁样行为的影响及其在大脑中的分子机制尚不清楚。在这项研究中,同伴交流被用作奖励,以研究奖励对 CUMS 诱导的抑郁样行为的影响,并通过高通量测序建立了来自具有抑郁样和弹性行为的小鼠的内侧前额叶皮层的 mRNA 和 miRNA 图谱。结果表明,伴随着同伴改善了 CUMS 诱导的小鼠抑郁样行为。此外,发现了 45 个与抑郁样行为相关的差异表达基因 (DEG)、8 个与弹性相关的 DEG 和 59 个与自然奖励 (同伴) 相关的 DEG,并发现了 196 个与同伴相关的差异表达 miRNA。基于差异表达的 miRNA 和 DEG 数据,建立了与同伴相关的 miRNA-mRNA 网络。总之,我们的数据为改善抑郁样行为提供了一种方法,并为预防或治疗抑郁症提供了许多潜在的药物靶点。

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