Studies on the altered expression of genes in the autopsy brain of people with schizophrenia

精神分裂症患者尸检大脑中基因表达改变的研究

• 批准号: 13470199
• 负责人: IKEDA Kazuhiko
• 金额: $ 8.26万
• 依托单位: Tokyo Metropolitan Organization for Medical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470199/
• 关键词: schizophrenia; bipolar mood disorder; DNA microarray; postmortem brain; neuropeptide Y; frontal cortex; Quantitative PCR; major depression; 剖検脳; 脂肪酸異常; 精神分裂病; 部検脳

To study the change of gene expression in the brain tissues of schizophrenia, we used the gene expression monitoring technology and compared two sets of pools containing each four RNA samples of frontal cortex that were randomly selected from the control or schizophrenia group. We found that the expression of two genes were commonly altered in four pairwise comparisons; the expression of DEAD-box protein p gene was increased and neuropeptide Y (NPY) gene expression was decreased in the schizophrenia group compared with the control group. To substantiate these results, we estimated their mRNA levels by the real time TaqMan method in the 15 samples of each frontal or temporal cortex of four matched groups of schizophrenia, bipolar disorder, major depression and normal control. A statistically significant decrease was observed for NPY in the frontal, but not in the temporal, cortex in the schizophrenia group (p = 0.003). A decrease was also observed in the frontal cortex of the bipolar disorder group (p = 0.031). In contrast, p72 gene expression showed no significant difference among the four groups. In conclusion, by novel technology of DNA array and TaqMan PCR analyses, we found that neuropeptide Y mRNA levels were significantly reduced in the frontal cortex in both schizophrenia and bipolar disorder.

为了研究精神分裂症患者脑组织中基因表达的变化，我们利用基因表达监测技术，比较了从对照组和精神分裂症组中随机选取的两组包含四个额叶皮质RNA样本的池。我们发现，在四个配对比较中，两个基因的表达普遍发生改变；与对照组相比，精神分裂症组DEAD-box蛋白p基因的表达增加，神经肽Y(NPY)基因的表达降低。为了证实这些结果，我们用实时TaqMan方法估计了精神分裂症、双相情感障碍、抑郁症和正常对照组四个匹配组的每个额叶或颞叶皮质的15个样本中它们的mRNA水平。精神分裂症组额叶皮质神经肽Y含量显著降低，而颞叶皮质神经肽Y含量无明显变化(p=0.003)。双相情感障碍组的额叶皮质也有减少(p=0.031)。四组间P72基因表达差异无统计学意义。综上所述，通过DNA阵列新技术和TaqMan聚合酶链式反应分析，我们发现精神分裂症和双相情感障碍患者额叶皮质神经肽Y基因表达水平均显著降低。

项目成果

Mizuguchi M et al.: "Loss of doublecortin from heterotopic gray matter of a fetus with subcortical laminar heterotopia"Neurology. 59. 143-144 (2002)

Mizuguchi M 等人：“皮质下层状异位胎儿异位灰质中双皮质素的丢失”神经病学。

Iwamoto K, Kakiuchi C, Bundo M, Ikeda K, Kato T: "Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders."Molecular Psychiatry. 9. 1-11 (2004)

Iwamoto K、Kakiuchi C、Bundo M、Ikeda K、Kato T：“通过比较主要精神障碍死后大脑的基因表达谱来表征双相情感障碍。”分子精神病学。

Ikeda K et al.: "Distribution of neuropeptide Y interneurons in the dorsal prefrontal cortex of schizophrenia."Proc Neuropsychopharmacol Biol Psychiatry. 28. 379-383 (2004)

Ikeda K 等人：“精神分裂症背侧前额皮质中神经肽 Y 中间神经元的分布。”Proc Neuropsychopharmacol Biol Psychiatry。

Mizuguchi M, Takashima S, Ikeda K, Kato M, Hori A.: "Loss of doublecortin from heterotopic gray matter of a fetus with subcortical laminar heterotopia."Neurology. 59. 143-144 (2002)

Mizuguchi M、Takashima S、Ikeda K、Kato M、Hori A.：“皮质下层状异位胎儿异位灰质中双皮质素的丢失。”神经病学。

Motoi Y, Takanashi M, Itaya M.Ikeda K.Mizuno Y, Mori H.: "Glial localization of four-repeat tau in atypical progressive supranuclear palsy."Neuropathology. 24. 6-65 (2004)

Motoi Y、Takanashi M、Itaya M.Ikeda K.Mizuno Y、Mori H.：“非典型进行性核上性麻痹中四重复 tau 蛋白的胶质定位。”神经病理学。