Schizophrenic Abnormality in Molecular Signaling and RNA Expression Profiling

精神分裂症分子信号传导和 RNA 表达谱异常

• 批准号: 12470035
• 负责人: NAWA Hiroyuki
• 金额: $ 4.03万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470035/
• 关键词: Mental disease; schizophrenia; cytokine; interleukin-1; RNA profiling; stress; EGF; TGF; HB EGF; 脳; 血清; 病態; 診断

Schizophrenia is a chronic mental disease and carries a variety of social problems. In spite of intensive studies on this illness, its diagnosis is only defined with DSM4, based on psychopathological symptoms but not any biological criteria. In the present study, we performed the RNA expression profiling and attempted to find biological markers for this illness. From postmortem samples of patients striatum, RNA was extracted and converted into CDNA probes for DMA array analysis. Among 3000 genes, mRNA for cytokines and their receptors was most markedly altered. Accordingly, we assessed protein changes in cytokines, interleukin-1 beta (IL-1 b) and interleukin-1 receptor antagonist (IL-1 RA). Both cytokines are implicated in stress reaction and known to increase in peripheral blood of schizophrenic patients. The postmortem study was carried out under the authorization of Niigata University Ethics Committee. Among the brain regions examined, protein levels for IL1 RA were significantly decreased in comparison with those in age-matched controls. In contrast, protein levels for IL-1b and IL-1 receptor exhibited no change in all the regions. Chronic haloperidol treatment of rats failed to influence IL-1RA levels in any of the brain regions. These observations suggest that the IL-1RA change in the prefrontal cortex reflects one of the pathological feature of schizophrenic patients, instead of their medications.

精神分裂症是一种慢性精神疾病，并带来各种社会问题。尽管对这种疾病进行了深入的研究，但其诊断仅根据DSM 4定义，基于精神病理学症状，而不是任何生物标准。在本研究中，我们进行了RNA表达谱分析，并试图找到这种疾病的生物标志物。从患者纹状体的死后样本中提取RNA并转化为cDNA探针用于DMA阵列分析。在3000个基因中，细胞因子及其受体的mRNA变化最明显。因此，我们评估了细胞因子、白细胞介素-1 β（IL-1 B）和白细胞介素-1受体拮抗剂（IL-1 RA）的蛋白质变化。这两种细胞因子都与应激反应有关，并且已知在精神分裂症患者的外周血中增加。尸检研究是在新泻大学伦理委员会的授权下进行的。在检查的大脑区域中，与年龄匹配的对照组相比，IL 1 RA的蛋白水平显著降低。相反，IL-1b和IL-1受体的蛋白水平在所有区域中均未显示变化。长期氟哌啶醇治疗大鼠未能影响IL-1 RA水平的任何大脑区域。这些观察结果表明，IL-1 RA在前额叶皮层的变化反映了精神分裂症患者的病理特征之一，而不是他们的药物治疗。

项目成果

Akiya Watakabe, et al.: "Similarity and variation in gene expression among human cerebral cortical subregions reveled by DNA macroarrays : Technical consideration of RNA expression profiling from postmortem samples"Mol. Brain Res. 88. 74-82 (2001)

Akiya Watakabe 等人：“DNA 宏阵列揭示的人类大脑皮层亚区域基因表达的相似性和变异：死后样本 RNA 表达谱的技术考虑”Mol。

Akiya Watakabe 他6名: "Similarity and variation in gene expression among human cerebral cortical subregions reveled by DNA macroarrays : Techinical consideration of RNA expression profiling from postmortem samples"Mol. Brain Res. 88. 74-82 (2001)

Akiya Watakabe 等 6 人：“DNA 宏阵列显示的人类大脑皮层亚区域基因表达的相似性和变异：死后样本 RNA 表达谱的技术考虑”Mol. 88. 74-82 (2001)

渡部雄一郎: "神経栄養因子・サイトカインと精神疾患"現代医療. 33巻. 2697-2702 (2001)

Yuichiro Watanabe：“神经营养因子/细胞因子和精神疾病”现代医学第 33 卷。2697-2702 (2001)

Takashi Futamura, et al.: "Abnormal expression of epidermal growth factor and its receptor in the forebrain and serum of schizophrenic patients"molecular Psychiatry. (in press). (2002)

Takashi Futamura等人：“精神分裂症患者前脑和血清中表皮生长因子及其受体的异常表达”分子精神病学。

Takashi Futamura 他9名: "Abnormal expression of epidermal growth factor and its receptor in the forebrain and serum of schizophrenic patients"Molecular Psychiatry. (in press). (2002)

Takashi Futamura 等 9 人：“精神分裂症患者前脑和血清中表皮生长因子及其受体的异常表达”《分子精神病学》（出版中）。