Identification of novel candidate genes for schizophrenia: using postmortem brain study

在我们2000年至2002年的科学研究（C）（2）项目中，我们发现精神分裂症动物模型和精神分裂症死后大脑中的几个信号转导系统发生了变化。此外，我们分析了精神分裂症死后大脑中的基因表达，以确定精神分裂症的新候选基因。1）我们发现，在甲基苯丙胺致敏大鼠的纹状体中，钙调磷酸酶蛋白减少，而磷酸苏氨酸-DARPP-32增加。这些结果表明，通过CaN的信号转导的活性在甲基致敏大鼠的纹状体中功能性降低。2）一种恶化的降钙素2A受体-G蛋白q α（Gq α）-磷酸肌醇特异性磷脂酶C β 1（PLC β 1）级联已被发现在左边，但不是右边，精神分裂症患者的上级颞叶皮层。3）我们筛选了NR 2B亚基基因编码羧基-在精神分裂症患者的细胞内末端结构域，并研究精神分裂症和NR 2B亚基基因的一个新的多态性之间的关联。发现1个沉默突变（2664 C/T）。2664 C/T基因型和等位基因频率在精神分裂症患者和健康对照组之间差异无统计学意义。对治疗动物和匹配对照的脑桥核的分析揭示了精神分裂症动物模型脑中与神经递质传递和细胞内传递相关的基因表达的变化。5）我们研究了精神分裂症患者脑区域的基因表达模式。cDNA阵列被用来筛选来自精神分裂症患者前额叶皮层的样本池。在检测的基因中，33个mRNA增加，22个mRNA减少。

In our Scientific Research (C)(2) project from 2000 to 2002, we found changes in several signal transduction systems in the brains of animal models for schizophrenia, and the postmortem brains of schizophrenia. In addition, we analyzed gene expression in the postmortem brains of schizophrenia, in order to identify novel candidate genes for schizophrenia.1) We found that calcineurin proteins decreased, while phosphothreonine-DARPP-32 increased in the striatum of Meth-sensitized rats. These results indicate that the activity of signal transduction via CaN is functionally decreased in the striatum of Meth-sensitized rats.2) A deteriorated serotonin2A receptor-G protein q alpha (Gq alpha) -phosphoinositide-specific phospholipase C beta1 (PLC beta1) cascade has been found in the left, but not right, the superior temporal cortex of patients with schizophrenia.3) We screened for genetic variations in the region of the NR2B subunit gene encoding the carboxyl-terminal intracellular domain in patients with schizophrenia and studied the association between schizophrenia and a novel polymorphism of the NR2B subunit gene. One silent mutation (2664C/T) was identified. No significant differences in the frequencies of 2664C/T genotypes and alleles were found between patients with schizophrenia and healthy comparison subjects.4) We searched for genes that are induced by phencyclidine using the mRNA differential-display technique. Analyses of the nucleus accumbens of the treated animals and matched controls revealed changes in the expression of genes related to glutamatergic transmission and the intracellular transmission in the brain of the animal model for schizophrenia.5) We investigated gene expression patterns in brain regions of patients with schizophrenia. A cDNA array was used to screen pools of samples from the prefrontal cortex of patients with schizophrenia. Of the examined genes, 33 mRNA were increased and 22 were decreased.