| 1 | Biol. Psychiatry 2007 Oct 62: 711-21 |
|---|---|
| PMID | 17568569 |
| 标题 | 精神分裂症前额叶皮质中与免疫和伴侣功能相关的基因表达增加的分子证据。 |
| Abstract | schizophrenia以复杂的基因表达变化为特征。前额叶皮层中的转录组改变已成为最近几项验尸研究的主题，这些研究既产生收敛性和发散发现。 为了提高测量精度，我们使用了具有长寡核苷酸的定制设计的DNA微阵列平台和带有重复的多个探针。该平台旨在评估特别选择的> 1800个基因的表达，因为它们在病理生理学中的假设作用schizophrenia. The gene expression differences in dorsolateral prefrontal cortex samples from 14 matched pairs ofschizophreniaand control subjects were analyzed with two technical replicates and four data mining approaches. 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 theschizophreniasamples. We speculate that the overexpression of SERPINA3, IFITM1, IFITM2,IFITM3，Chi3L1，MT2A，CD14，HSPB1，HSPA1B和HSPA1Aschizophreniasubjects represents a long-lasting and correlated signature of an early environmental insult during development that actively contributes to the pathophysiology of prefrontal dysfunction. |
| SCZ关键字 | schizophrenia, schizophrenic |
| 2 | BMC Psychiatry 2007 -1 7：46 |
| PMID | 17822540 |
| 标题 | 精神分裂症大脑中上调的炎症相关基因。 |
| Abstract | Multiple studies have shown that brain gene expression is disturbed in subjects suffering fromschizophrenia. However, disentangling disease effects from alterations caused by medication is a challenging task. The main goal of this study is to find transcriptional alterations inschizophreniathat are independent of neuroleptic treatment. We compared the transcriptional profiles in brain autopsy samples from 55 control individuals with that from 55schizophrenicsubjects, subdivided according to the type of antipsychotic medication received. 使用全球和高分辨率mRNA定量技术，我们表明与免疫反应有关的基因（GO：0006955）在所有患者组中受到调节，包括在死亡时未接受治疗的患者。特别是，ifitm2，IFITM3, SERPINA3, and GBP1 showed increased mRNA levels inschizophrenia（来自qpcr <或= 0.01的p值）。这四个基因在这两个基因中均共表达schizophrenicsubjects and controls. In-vitro experiments suggest that these genes are expressed in both oligodendrocyte and endothelial cells, where transcription is inducible by the inflammatory cytokines TNF-alpha, IFN-alpha and IFN-gamma. Although the modified genes are not classical indicators of chronic or acute inflammation, our results indicate alterations of inflammation-related pathways inschizophrenia. In addition, the observation in oligodendrocyte cells suggests that alterations in inflammatory-related genes may have consequences for myelination. Our findings encourage future research to explore whether anti-inflammatory agents can be used in combination with traditional antipsychotics for a more efficient treatment ofschizophrenia. |
| SCZ关键字 | schizophrenia, schizophrenic |
| 3 | BMC Psychiatry 2007 -1 7：46 |
| PMID | 17822540 |
| 标题 | 精神分裂症大脑中上调的炎症相关基因。 |
| Abstract | Multiple studies have shown that brain gene expression is disturbed in subjects suffering fromschizophrenia. However, disentangling disease effects from alterations caused by medication is a challenging task. The main goal of this study is to find transcriptional alterations inschizophreniathat are independent of neuroleptic treatment. We compared the transcriptional profiles in brain autopsy samples from 55 control individuals with that from 55schizophrenicsubjects, subdivided according to the type of antipsychotic medication received. 使用全球和高分辨率mRNA定量技术，我们表明与免疫反应有关的基因（GO：0006955）在所有患者组中受到调节，包括在死亡时未接受治疗的患者。特别是，ifitm2，IFITM3, SERPINA3, and GBP1 showed increased mRNA levels inschizophrenia（来自qpcr <或= 0.01的p值）。这四个基因在这两个基因中均共表达schizophrenicsubjects and controls. In-vitro experiments suggest that these genes are expressed in both oligodendrocyte and endothelial cells, where transcription is inducible by the inflammatory cytokines TNF-alpha, IFN-alpha and IFN-gamma. Although the modified genes are not classical indicators of chronic or acute inflammation, our results indicate alterations of inflammation-related pathways inschizophrenia. In addition, the observation in oligodendrocyte cells suggests that alterations in inflammatory-related genes may have consequences for myelination. Our findings encourage future research to explore whether anti-inflammatory agents can be used in combination with traditional antipsychotics for a more efficient treatment ofschizophrenia. |
| SCZ关键字 | schizophrenia, schizophrenic |
| 4 | Nihon Shinkei Seishin Yakurigaku Zasshi 2013 Aug 33: 149-54 |
| PMID | 25069250 |
| 标题 | [Perinatal innate immune activation and neuropsychological development]. |
| Abstract | Development of animal models is a crucial issue in biological psychiatry for the search of novel drug targets as well as the screening of candidate compounds. Epidemiologic studies suggest that environmental insults, such as prenatal infection and perinatal complication, are involved in the development ofschizophrenia. Recently, we have developed a novel mouse model of viral infection during the perinatal stage by injecting polyriboinosinic-polyribocytidilic acid (polyI:C) into neonatal mice. Neonatal treatment of mice with polyI:C, an inducer of innate immune responses via toll-like receptor 3, caused a significant increase in interferon-induced transmembrane protein 3 (IFITM3) levels in the astrocytes of the hippocampus, which resulted in long-lasting brain dysfunction, including cognitive and emotional impairments as well as a deficit in depolarization-evoked glutamate release in the hippocampus in adulthood. Neonatal polyI:C-induced neuronal impairments have not been observed inIFITM3-KO mice. These findings suggest that the induction ofIFITM3expression in astrocytes by the activation of the innate immune system during the early stages of neurodevelopment has non-cell autonomous effects that affect subsequent neurodevelopment, leading to neuropathological impairments and brain dysfunction, by impairing endocytosis in astrocytes. |
| SCZ关键字 | schizophrenia, schizophrenic |
| 5 | Transl Psychiatry 2013 -1 3: e321 |
| PMID | 24169640 |
| 标题 | 通过mRNA测序进行基因表达分析表明，精神分裂症个体的海马中免疫/炎症相关基因的表达增加。 |
| Abstract | 验尸脑组织中的全基因组表达分析最近提供了对schizophrenia. Previous microarray and RNA-Seq studies identified several biological processes including synaptic function, mitochondrial function and immune/inflammation response as altered in the cortex of subjects withschizophrenia. Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes inschizophreniacases as compared with unaffected controls. Immune/inflammation response was the main biological process over-represented in these genes. The upregulation of several of these genes, IFITM1, IFITM2,IFITM3, APOL1 (Apolipoprotein L1), ADORA2A (adenosine receptor 2A), IGFBP4 and CD163 were validated in theschizophrenia使用来自SNCID数据库和定量RT-PCR的数据的受试者。我们确定了与schizophrenia其中包括与免疫/炎症反应以及海马中含白蛋白神经元的密度有关的大多数差异表达基因。结果表明，海马中的异常免疫/炎症反应可能是病理生理的基础schizophrenia并且可能与导致疾病认知缺陷的含白蛋白神经元的异常有关。 |
| SCZ关键字 | schizophrenia, schizophrenic |
| 6 | Biol. Psychiatry 2014 Feb 75: 316-23 |
| PMID | 23890736 |
| 标题 | 精神分裂症的免疫系统障碍。 |
| Abstract | Epidemiological, genetic, transcriptome, postmortem, peripheral biomarker, and therapeutic studies ofschizophrenia所有人都表明疾病中先天和适应性免疫系统的失调，这些免疫变化可能会积极促进疾病症状。受试者大脑中的基因表达干扰schizophreniashow complex, region-specific changes with consistently replicated and potentially interdependent induction of serpin peptidase inhibitor, clade A member 3 (SERPINA3) and interferon inducible transmembrane protein (IFITM) family transcripts in the prefrontal cortex. Recent data suggest thatIFITM3表达是母体免疫激活的关键介体。因为IFITM基因家族主要在内皮细胞和脑膜中表达，并且由于脑膜在间神经元发育中起关键作用，因此我们建议这两个非神经元细胞群可能在疾病病理生理学中起重要作用。最后，我们建议IFITM3特别是可能是一个小说,吸引人,知识ge-based drug target for treatment ofschizophrenia. |
| SCZ关键字 | schizophrenia, schizophrenic |