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慢性社会挫败应激模型 C57BL/6J 雄性小鼠纹状体与昆明小鼠肠道菌群失调模型的比较转录组学分析。

Comparative transcriptional analyses of the striatum in the chronic social defeat stress model in C57BL/6J male mice and the gut microbiota-dysbiosis model in Kumming mice.

机构信息

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; The Jin Feng Laboratory, Chongqing 401329, China.

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; The Jin Feng Laboratory, Chongqing 401329, China.

出版信息

Neuroscience. 2024 Dec 6;562:217-226. doi: 10.1016/j.neuroscience.2024.10.057. Epub 2024 Nov 1.

DOI:10.1016/j.neuroscience.2024.10.057
PMID:39489477
Abstract

Depression is a complex disorder with multiple contributing factors, and chronic stress has previously been recognized as a major causative factor, while gut microbes have also been found to be involved in depression recently. However, gene expression in depression models with different etiologies is unclear. Here, we compared the transcriptomes of the striatum in chronic social defeat stress (CSDS) model of C57BL/6J male mice and fecal microbiota transplant (FMT) model of Kumming male mice. We found that the proportion of shared differentially expressed genes (DEGs) between the two models was only 24 %. The specific DEGs of FMT model were enriched in immune and inflammatory, and are associated with changes in vascular and ciliated ependymal cells. The specific DEGs of CSDS model were enriched in neuron and synapse. The results of network analysis suggested the expression patterns and biological function of depressive-like behaviors-related modules in the two models are different. Further, the alternative splicing events of CSDS are more than FMT. Our results suggested models of depression induced by different etiologies differ significantly in gene expression and biological function. Our study also suggested us to pay attention to the characteristics of models of depression of different etiologies and provided a more comprehensive understanding of the heterogeneity of depression.

摘要

抑郁症是一种复杂的疾病,有多种致病因素,慢性应激以前被认为是一个主要的致病因素,而肠道微生物最近也被发现与抑郁症有关。然而,不同病因的抑郁症模型中的基因表达尚不清楚。在这里,我们比较了慢性社会挫败应激(CSDS)模型的 C57BL/6J 雄性小鼠纹状体和粪便微生物移植(FMT)模型的昆明雄性小鼠的转录组。我们发现,两种模型之间共享差异表达基因(DEG)的比例仅为 24%。FMT 模型的特定 DEG 富集在免疫和炎症中,与血管和纤毛室管膜细胞的变化有关。CSDS 模型的特定 DEG 富集在神经元和突触中。网络分析的结果表明,两种模型中与抑郁样行为相关模块的表达模式和生物学功能不同。此外,CSDS 的选择性剪接事件比 FMT 多。我们的研究结果表明,不同病因引起的抑郁症模型在基因表达和生物学功能上存在显著差异。我们的研究还提示我们要注意不同病因的抑郁症模型的特点,为抑郁症的异质性提供了更全面的认识。

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