Abstract

Structural changes in the corpus callosum have been reported in schizophrenia; however, the underlying molecular mechanism remains unclear. As the corpus callosum is high in lipid content, we analyzed the lipid contents of the corpora callosa from 15 patients with schizophrenia and 15 age- and sex-matched controls using liquid chromatography coupled to tandem mass spectrometry and identified lipid combinations associated with schizophrenia. Real-time quantitative polymerase chain reaction analyses using extended samples (schizophrenia, n = 95; control, n = 91) showed low expression levels of lipid metabolism-related genes and their potential upstream transcription factors in schizophrenia. Subsequent pathway analysis identified a gene regulatory network where nuclear factor of activated T cells 2 (NFATC2) is placed most upstream. We also observed low gene expression levels of microglial markers, inflammatory cytokines, and colony-stimulating factor 1 receptor (CSF1R), which is known to regulate the density of microglia, in the corpus callosum in schizophrenia. The interactions between CSF1R and several genes in the presently identified gene network originating from NFATC2 have been reported. Collectively, this study provides evidence regarding lipid abnormalities in the corpora callosa of patients with schizophrenia and proposes the potential role of impaired “NFATC2-relevant gene network-microglial axis” as its underlying mechanism.

中文翻译：

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精神分裂症胼胝体的脂质病理学和异常基因调控网络与小胶质细胞标志物表达减少的潜在作用。

摘要

据报道，精神分裂症患者胼胝体的结构变化；然而，潜在的分子机制仍不清楚。由于胼胝体脂质含量高，我们使用液相色谱与串联质谱联用分析了 15 名精神分裂症患者和 15 名年龄和性别匹配的对照的胼胝体的脂质含量，并确定了与精神分裂症相关的脂质组合。使用扩展样本进行实时定量聚合酶链反应分析（精神分裂症，n  = 95；对照，n = 91) 显示精神分裂症中脂质代谢相关基因及其潜在上游转录因子的低表达水平。随后的通路分析确定了一个基因调控网络，其中活化 T 细胞的核因子 2 ( NFATC2 ) 位于最上游。我们还观察到精神分裂症患者胼胝体中小胶质细胞标志物、炎性细胞因子和集落刺激因子 1 受体 ( CSF1R ) 的低基因表达水平，CSF1R已知可调节小胶质细胞的密度。CSF1R与目前鉴定的源自NFATC2 的基因网络中的几个基因之间的相互作用已经汇报过。总的来说，这项研究提供了关于精神分裂症患者的语料略萨血脂异常的证据，并提出损害“的潜在作用NFATC2度相关的基因网络的小胶质细胞轴”作为其基础的机制。