Identifying Antidepressant Effects of Brain-Derived Neurotrophic Factor and IDO1 in the Mouse Model Based on RNA-Seq Data.
Identifying Antidepressant Effects of Brain-Derived Neurotrophic Factor and IDO1 in the Mouse Model Based on RNA-Seq Data.
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基于 RNA-Seq 数据鉴定小鼠模型中脑源性神经营养因子和 IDO1 的抗抑郁作用
DOI：
10.3389/fgene.2022.890961
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发表时间：
2022
影响因子：
3.7
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Ren J;Li C;Wei S;He Y;Huang P;Xu J
脑源性神经营养因子（BDNF）的缺失和吲哚胺2，3-双加氧酶1（IDO 1）的上调与动物抑郁症的严重程度相关。在转录组水平上抑郁的神经递质假说可以使用BDNF和IDO 1敲除小鼠模型和RNA-seq进行测试。在本研究中，开发了BDNF+/−、IDO 1-/−和慢性超轻度应激（CHUOS）诱导的抑郁症小鼠模型和对照，并分析了差异表达的基因。此外，使用ceRNA包在lncRNA 2 Target数据库中搜索潜在的lncRNA。最后，使用STRINGdb构建了蛋白质-蛋白质相互作用（PPI）网络。通过比较对照组和CANS模型组，发现途径富集分析和ceRNA网络分析显示，大多数差异表达基因（DEG）与保护脆弱的神经元回路有关。此外，当比较对照组和BDNF+/−模型组时，我们发现富集的通路与神经系统发育和突触组织相关。当复制临床患者的神经递质破坏特征时，这种比较揭示了BDNF敲除模型和BDNF敲除模型之间的显著差异，BDNF+/−模型可能上级经典的BDNF敲除模型。本研究中获得的数据暗示了与抑郁症相关的三种小鼠模型中的潜在DEG及其富集途径以及ceRNA网络介导的基因在抑郁症进展中的调节。总之，我们的发现可能对揭示动物抑郁症神经递质假说的机制至关重要。
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.
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影响因子：
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