Song Zhenhua, Wang Jin-Hui
Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Psychiatry. 2021 Mar 31;12:634933. doi: 10.3389/fpsyt.2021.634933. eCollection 2021.
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.
在慢性应激状态下,抑郁样行为的出现可能与长期缺乏奖励导致大脑奖赏回路功能下降有关。然而,奖赏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仍知之甚少。在此,采用陪伴来模拟一种奖赏,以研究奖赏对慢性不可预测轻度应激(CUMS)诱导的抑郁样行为的影响,并利用高通量测序分析从表现出抑郁样行为和具有恢复力行为的小鼠中采集的腹侧被盖区(VTA)中的miRNA和mRNA谱。我们观察到,在小鼠中,陪伴可改善CUMS诱导的抑郁样行为,发现202个差异表达基因(DEGs)与抑郁样行为相关,27个DEGs与恢复力相关,159个DEGs与陪伴相关。重要的是,我们还获得了228个与陪伴相关的差异表达miRNA。此外,基于miRNA和mRNA谱,在腹侧被盖区建立了与陪伴相关的miRNA-mRNA网络。总之,我们的结果揭示了一种改善抑郁样行为的新方法,以及许多预防或治疗抑郁症的潜在药物靶点。