Kim S, Hwang Y, Lee D, Webster M J
Stanley Brain Research Laboratory, Stanley Medical Research Institute, Rockville, MD, USA.
Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.
Transl Psychiatry. 2016 Nov 29;6(11):e964. doi: 10.1038/tp.2016.229.
The choroid plexus (CP) has a key role in maintaining brain homeostasis by producing cerebrospinal fluid (CSF), by mediating transport of nutrients and removing metabolic products from the central nervous system and by responding to peripheral inflammatory signals. Although abnormal markers of immune response and inflammation are apparent in individuals with schizophrenia, the CP of these individuals has not been characterized. We therefore sequenced mRNA from the CP from two independent collections of individuals with schizophrenia and unaffected controls. Genes related to immune function and inflammation were upregulated in both collections. In addition, a co-expression module related to immune/inflammation response that was generated by combining mRNA-Seq data from both collections was significantly associated with disease status. The immune/inflammation-related co-expression module was positively correlated with levels of C-reactive protein (CRP), cortisol and several immune modulator proteins in the serum of the same individuals and was also positively correlated with CRP, cortisol and pro-inflammatory cytokines in the frontal cortex of the same individuals. In addition, we found a substantial number of nodes (genes) that were common to our schizophrenia-associated immune/inflammation module from the pooled data and a module we generated from lippopolysaccharides-treated mouse model data. These results suggest that the CP of individuals with schizophrenia are responding to signals from the periphery by upregulating immune/inflammation-related genes to protect the brain and maintain the homeostasis but nevertheless fails to completely prevent immune/inflammation related changes in the brain.
脉络丛（CP）在维持脑内环境稳定方面发挥着关键作用，它通过产生脑脊液（CSF）、介导营养物质的运输以及清除中枢神经系统的代谢产物，并对外周炎症信号作出反应来实现这一功能。尽管免疫反应和炎症的异常标志物在精神分裂症患者中很明显，但这些患者的脉络丛尚未得到特征描述。因此，我们对来自两个独立的精神分裂症患者和未受影响对照人群的脉络丛mRNA进行了测序。在这两个群体中，与免疫功能和炎症相关的基因均上调。此外，通过合并两个群体的mRNA测序数据生成的一个与免疫/炎症反应相关的共表达模块与疾病状态显著相关。该免疫/炎症相关共表达模块与同一人群血清中的C反应蛋白（CRP）、皮质醇和几种免疫调节蛋白水平呈正相关，也与同一人群额叶皮质中的CRP、皮质醇和促炎细胞因子呈正相关。此外，我们发现从汇总数据中得到的与精神分裂症相关的免疫/炎症模块和我们从脂多糖处理的小鼠模型数据中生成的一个模块有大量共同的节点（基因）。这些结果表明，精神分裂症患者的脉络丛通过上调免疫/炎症相关基因来对外周信号作出反应，以保护大脑并维持内环境稳定，但仍未能完全防止大脑中与免疫/炎症相关的变化。
