Schizophrenic Abnormality in Molecular Signaling and RNA Expression Profiling

精神分裂症是一种慢性精神疾病，会带来各种社会问题。尽管对这种疾病进行了深入的研究，但它的诊断只能用DSM4来定义，基于精神病理症状，而不是任何生物学标准。在本研究中，我们进行了RNA表达谱分析，并试图寻找这种疾病的生物标志物。从患者死后纹状体标本中提取RNA，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变化最为明显。因此，我们评估了细胞因子、白介素1β(IL-1b)和白介素1受体拮抗剂(IL-1RA)的蛋白质变化。这两种细胞因子都与应激反应有关，并已知在精神分裂症患者的外周血液中会增加。尸检研究是在新泻大学伦理委员会的授权下进行的。在被检测的脑区中，与年龄匹配的对照组相比，IL1RA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都没有变化。慢性氟哌啶醇治疗大鼠未能影响任何脑区的IL-1RA水平。这些观察表明，前额叶皮质IL-1RA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。

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.