Microglia Transcriptome Changes in a Model of Depressive Behavior after Immune Challenge
Microglia Transcriptome Changes in a Model of Depressive Behavior after Immune Challenge
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DOI：
10.1371/journal.pone.0150858
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发表时间：
2016-03-09
期刊：
影响因子：
3.7
通讯作者：
Rodriguez-Zas, Sandra L.
中科院分区：
文献类型：
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作者：
Gonzalez-Pena, Dianelys;Nixon, Scott E.;Rodriguez-Zas, Sandra L.
据报道，在疾病康复后，对挑战的免疫反应后出现抑郁症状。进行了炎症相关抑郁行为模型中小胶质细胞转录组失调的RNA-Seq研究。将卡介苗（BCG）攻击后第7天来自小鼠的小胶质细胞的转录组与来自未攻击的对照小鼠的转录组以及来自相同小鼠的外周巨噬细胞的转录组进行比较。在BCG攻击小鼠和对照小鼠分别在小胶质细胞和巨噬细胞中差异表达的562和3，851个基因中，353个基因在这些细胞类型之间重叠。在小胶质细胞中最差异表达的基因中，血清淀粉样蛋白A3（Saa 3）和细胞粘附分子3（Cadm 3）在BCG激发的小胶质细胞中过表达，而含有卷曲螺旋结构域162（Ccdc 162）和肌联蛋白帽（Tcap）在BCG激发的小胶质细胞中表达不足。BCG激发小鼠和对照小鼠之间的许多差异表达基因与包括抑郁症状在内的神经系统疾病相关。在细胞类型中，S100钙结合蛋白A9（S100 A9）、白细胞介素1 β（IIIb）和犬尿氨酸3-单加氧酶（Kmo）在激发小鼠和对照小鼠之间差异表达。免疫应答、趋化性和趋化因子活性是由差异表达基因富集的功能类别。在细胞类型之间差异表达的9，117个基因中富集的功能类别包括白细胞调节和活化、趋化因子和细胞因子活性、MAP激酶活性和细胞凋亡。超过200个基因表现出细胞类型之间的选择性剪接事件，包括WNK赖氨酸缺陷蛋白激酶1（Wnk 1）和微管肌动蛋白交联因子1（Macf 1）。网络可视化揭示了小胶质细胞在疾病症状消退后仍表现出响应免疫挑战的转录组失调的能力，尽管低于在巨噬细胞中观察到的能力。小胶质细胞中的持续性转录组失调与神经系统疾病共享模式，表明相关的持续性抑郁症状共享共同的转录组基础。
Depression symptoms following immune response to a challenge have been reported after the recovery from sickness. A RNA-Seq study of the dysregulation of the microglia transcriptome in a model of inflammation-associated depressive behavior was undertaken. The transcriptome of microglia from mice at day 7 after Bacille Calmette Guerin (BCG) challenge was compared to that from unchallenged Control mice and to the transcriptome from peripheral macrophages from the same mice. Among the 562 and 3,851 genes differentially expressed between BCG-challenged and Control mice in microglia and macrophages respectively, 353 genes overlapped between these cells types. Among the most differentially expressed genes in the microglia, serum amyloid A3 (Saa3) and cell adhesion molecule 3 (Cadm3) were over-expressed and coiled-coil domain containing 162 (Ccdc162) and titin-cap (Tcap) were under-expressed in BCG-challenged relative to Control. Many of the differentially expressed genes between BCG-challenged and Control mice were associated with neurological disorders encompassing depression symptoms. Across cell types, S100 calcium binding protein A9 (S100A9), interleukin 1 beta (ll1b) and kynurenine 3-monooxygenase (Kmo) were differentially expressed between challenged and control mice. Immune response, chemotaxis, and chemokine activity were among the functional categories enriched by the differentially expressed genes. Functional categories enriched among the 9,117 genes differentially expressed between cell types included leukocyte regulation and activation, chemokine and cytokine activities, MAP kinase activity, and apoptosis. More than 200 genes exhibited alternative splicing events between cell types including WNK lysine deficient protein kinase 1 (Wnk1) and microtubule-actin crosslinking factor 1 (Macf1). Network visualization revealed the capability of microglia to exhibit transcriptome dysregulation in response to immune challenge still after resolution of sickness symptoms, albeit lower than that observed in macrophages. The persistent transcriptome dysregulation in the microglia shared patterns with neurological disorders indicating that the associated persistent depressive symptoms share a common transcriptome basis.