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正常老年人大脑额叶中的共表达网络与精神分裂症。

Shared co-expression networks in frontal cortex of the normal aged brain and schizophrenia.

机构信息

Stanley Brain Research Laboratory, Stanley Medical Research Institute, 9800 Medical Center Drive, Rockville, MD 20850, United States of America.

Department of Bio and Brain Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea.

出版信息

Schizophr Res. 2019 Feb;204:253-261. doi: 10.1016/j.schres.2018.09.010. Epub 2018 Sep 15.

Abstract

Previous studies on the brain of people with schizophrenia have identified structural changes and gene expression changes, suggesting that brain aging maybe accelerated in people with schizophrenia. To better characterize gene expression profiles in schizophrenia and in the aged population we constructed co-expression networks using RNA-Seq data from frontal cortex. The first data set analysed was from 62 subjects with schizophrenia and 51 unaffected controls ranging in age from 19 to 63 years. The second separate data set was from normal control individuals ranging in age from 29 to 106 years. In the first data set, we found two co-expression modules significantly associated with schizophrenia. One was a downregulated co-expression module enriched for neuron function related genes and the other was an upregulated immune/inflammation-related module. In the second data set of normal individuals, we found seven co-expression modules significantly correlated with age. A comparison of the co-expression modules from the two data sets revealed a significant consensus in nodes associated with schizophrenia and those associated with normal aging. The results indicate that a co-expression module related to neuronal function is downregulated and an immune/inflammation related co-expression module is upregulated, and associated with cells of the blood vessels, in both schizophrenia and in normal aging. This finding adds further support to the hypothesis that there may be accelerated brain aging in schizophrenia.

摘要

先前对精神分裂症患者大脑的研究已经确定了结构变化和基因表达变化,这表明精神分裂症患者的大脑衰老可能加速。为了更好地描述精神分裂症患者和老年人群中的基因表达谱,我们使用来自额叶皮层的 RNA-Seq 数据构建了共表达网络。第一个分析的数据来自 62 名精神分裂症患者和 51 名未受影响的对照组,年龄在 19 岁至 63 岁之间。第二个独立的数据来自年龄在 29 岁至 106 岁之间的正常对照个体。在第一个数据集中,我们发现了两个与精神分裂症显著相关的共表达模块。一个是下调的共表达模块,富含与神经元功能相关的基因,另一个是上调的免疫/炎症相关模块。在第二个正常个体的数据集中,我们发现了七个与年龄显著相关的共表达模块。对两个数据集的共表达模块进行比较,发现与精神分裂症相关的节点与与正常衰老相关的节点存在显著共识。结果表明,与神经元功能相关的共表达模块下调,与免疫/炎症相关的共表达模块上调,并与血管细胞相关,这在精神分裂症和正常衰老中都存在。这一发现进一步支持了大脑衰老在精神分裂症中可能加速的假说。

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