Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia
Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia
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DOI：
10.1016/j.biopsych.2006.12.021
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发表时间：
2007-10-01
影响因子：
10.6
通讯作者：
Mirnics, Karoly
中科院分区：
文献类型：
--
作者：
Arion, Dominique;Unger, Travis;Mirnics, Karoly
背景：精神分裂症的特点是复杂的基因表达变化。在前额叶皮层的转录组的改变一直是最近的几个尸检研究，产生收敛和发散findings.Methods的主题：为了提高测量精度，我们使用了定制设计的DNA微阵列平台与长的寡核苷酸和多个探针的重复。该平台被设计用于评估> 1800个基因的表达，这些基因是由于它们在精神分裂症的病理生理学中的假设作用而专门选择的。采用两种技术重复和四种数据挖掘方法分析了14对配对的精神分裂症患者和对照组患者的背外侧前额叶皮层样本中的基因表达差异。结果：除了复制突触、少突胶质细胞和信号转导基因中的许多表达变化外，我们还发现并验证了精神分裂症样本中免疫/伴侣转录物的稳健上调。我们推测，精神分裂症受试者中SERPINA 3、IFITM 1、IFITM 2、IFITM 3、CHI 3L 1、MT 2A、CD 14、HSPB 1、HSPA 1B和HSPA 1A的过表达代表了发育过程中早期环境损伤的持久和相关特征，其积极促进了前额叶功能障碍的病理生理学。
Background: Schizophrenia is characterized by complex gene expression changes. The transcriptome alterations in the prefrontal cortex have been the subject of several recent postmortem studies that yielded both convergent and divergent findings.Methods: To increase measurement precision, we used a custom-designed DNA microarray platform with long oligonucleotides and multiple probes with replicates. The platform was designed to assess the expression of > 1800 genes specifically chosen because of their hypothesized roles in the pathophysiology of schizophrenia. The gene expression differences in dorsolateral prefrontal cortex samples from 14 matched pairs of schizophrenia and control subjects were analyzed with two technical replicates and four data mining approaches.Results: In addition to replicating many expression changes in synaptic, oligodendrocyte, and signal transduction genes, we uncovered and validated a robust immune/chaperone transcript upregulation in the schizophrenia samples.Conclusions: We speculate that the overexpression of SERPINA3, IFITM1, IFITM2, IFITM3, CHI3L1, MT2A, CD14, HSPB1, HSPA1B, and HSPA1A in schizophrenia subjects represents a long-lasting and correlated signature of an early environmental insult during development that actively contributes to the pathophysiology of prefrontal dysfunction.