Table1_Identifying Antidepressant Effects of Brain-Derived Neurotrophic Factor and IDO1 in the Mouse Model Based on RNA-Seq Data.XLSX

Deletion of brain-derived neurotrophic factor (BDNF) and upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) are associated with depression severity in animals. The neurotransmitter hypothesis of depression at the transcriptomic level can be tested using BDNF- and IDO1-knockout mouse models and RNA-seq. In this study, BDNF+/−, IDO1−/−, and chronic ultra-mild stress (CUMS)-induced depression mouse models and controls were developed, and the differentially expressed genes were analyzed. Furthermore, the ceRNA package was used to search the lncRNA2Target database for potential lncRNAs. Finally, a protein–protein interaction (PPI) network was constructed using STRINGdb. By comparing the control and CUMS model groups, it was found that pathway enrichment analysis and ceRNA network analysis revealed that most differentially expressed genes (DEGs) were associated with protection of vulnerable neuronal circuits. In addition, we found the enriched pathways were associated with nervous system development and synapse organization when comparing the control and BDNF+/−model groups. When replicating the neurotransmitter disruption features of clinical patients, such comparisons revealed the considerable differences between CUMS and knockdown BDNF models, and the BDNF+/−model may be superior to the classic CUMS model. The data obtained in the present study implicated the potential DEGs and their enriched pathway in three mouse models related to depression and the regulation of the ceRNA network-mediated gene in the progression of depression. Together, our findings may be crucial for uncovering the mechanisms underlying the neurotransmitter hypothesis of depression in animals.

脑源性神经营养因子（BDNF）的缺失及吲哚amine 2,3-双加氧酶1（IDO1）的上调与动物抑郁症的严重程度密切相关。通过转录组水平对抑郁症的神经递质假说进行验证，可利用BDNF-和IDO1敲除小鼠模型以及RNA测序技术。在本研究中，构建了BDNF+/−、IDO1−/−以及慢性轻度应激（CUMS）诱导的抑郁症小鼠模型及其对照组，并对差异表达基因进行了分析。此外，利用ceRNA软件包在lncRNA2Target数据库中搜索潜在的lncRNA。最终，通过STRINGdb构建了蛋白质-蛋白质相互作用（PPI）网络。通过比较对照组与CUMS模型组，发现通路富集分析和ceRNA网络分析显示，大多数差异表达基因（DEGs）与脆弱神经元电路的保护相关。此外，当对比对照组与BDNF+/−模型组时，富集的通路与神经系统发育和突触组织相关。在复制临床患者神经递质破坏特征时，此类比较揭示了CUMS与敲低BDNF模型之间的显著差异，BDNF+/−模型可能优于经典的CUMS模型。本研究获得的数据暗示了与抑郁症及其ceRNA网络介导的基因调控相关的潜在DEGs及其富集通路。综上所述，我们的发现对于揭示动物抑郁症神经递质假说背后的机制可能至关重要。