Table_6_miRNA and mRNA Profiles in Ventral Tegmental Area From Juvenile Mice With Companion Communication of Improving CUMS-Induced Depression-Like Behaviors.XLS

Under chronic stress, the appearance of depression-like behaviors may be related to the decline of the brain's reward circuit function which caused by long-term lack of reward. However, the effect of reward treatment on depressive-like behaviors induced by chronic stress and its molecular mechanism in the brain remain poorly understood. Here, accompanying with companion was used to imitate a reward to study the effect of reward on depression-like behaviors induced by chronic unpredicted mild stress (CUMS), and high-throughput sequencing was used to analyze the miRNA and mRNA profiles in ventral tegmental area (VTA) harvested from depression-like and resilient behaviors mice. We observed that CUMS-induced depression-like behaviors were ameliorated by accompanying with companion in mice, and 202 differentially expressed genes (DEGs) were found to be associated with depression-like behaviors, 27 DEGs associated with resilience, 159 DEGs associated with accompanying with companion. Importantly, we also obtained 228 differentially expressed miRNAs that associated with accompanying with companion. Furthermore, the miRNA-mRNA network associated with companion was established in ventral tegmental area, based on the miRNA and mRNA profiles. Altogether, our results uncover a new way to ameliorate depression-like behavior, as well as many potential drug targets to prevent or treat depression.

在慢性应激条件下，类抑郁行为的发生可能与长期奖赏缺失引发的大脑奖赏回路功能减退密切相关。然而，奖赏干预对慢性应激诱导的类抑郁行为的调控作用及其脑内分子机制，目前仍未得到充分阐明。本研究以同伴陪伴作为奖赏干预手段，探究其对慢性不可预见性温和应激（chronic unpredicted mild stress, CUMS）诱导的小鼠类抑郁行为的改善效果，并通过高通量测序技术，分析从抑郁样行为小鼠与抗压行为小鼠中采集的腹侧被盖区（ventral tegmental area, VTA）内的微小RNA（microRNA, miRNA）与信使RNA（messenger RNA, mRNA）表达谱。研究结果显示，同伴陪伴可显著改善慢性应激诱导的小鼠类抑郁行为；筛选得到202个与类抑郁行为相关的差异表达基因（differentially expressed genes, DEGs）、27个与抗压表型相关的DEGs，以及159个与同伴陪伴干预相关的DEGs。此外，本研究还筛选得到228个与同伴陪伴干预相关的差异表达miRNA。进一步基于上述miRNA与mRNA表达谱，在腹侧被盖区中构建了与同伴陪伴相关的miRNA-mRNA调控网络。综上，本研究不仅揭示了一种改善类抑郁行为的全新策略，同时筛选得到多个可用于抑郁症预防与治疗的潜在药物靶点。