Colantuoni Carlo, Hyde Thomas M, Mitkus Shruti, Joseph Andrew, Sartorius Leah, Aguirre Claudia, Creswell Johanna, Johnson Elizabeth, Deep-Soboslay Amy, Herman Mary M, Lipska Barbara K, Weinberger Daniel R, Kleinman Joel E
Clinical Brain Disorders Branch, Genes Cognition and Psychosis Program, IRP, NIMH, NIH, Bethesda, MD 20892, USA.
Brain Struct Funct. 2008 Sep;213(1-2):255-71. doi: 10.1007/s00429-008-0181-5. Epub 2008 May 10.
The molecular basis of complex neuropsychiatric disorders most likely involves many genes. In recent years, specific genetic variations influencing risk for schizophrenia and other neuropsychiatric disorders have been reported. We have used custom DNA microarrays and qPCR to investigate the expression of putative schizophrenia susceptibility genes and related genes of interest in the normal human brain. Expression of 31 genes was measured in Brodmann's area 10 (BA10) in the prefrontal cortex of 72 postmortem brain samples spanning half a century of human aging (18-67 years), each without history of neuropsychiatric illness, neurological disease, or drug abuse. Examination of expression across age allowed the identification of genes whose expression patterns correlate with age, as well as genes that share common expression patterns and that possibly participate in common cellular mechanisms related to the emergence of schizophrenia in early adult life. The expression of GRM3 and RGS4 decreased across the entire age range surveyed, while that of PRODH and DARPP-32 was shown to increase with age. NRG1, ERBB3, and NGFR show expression changes during the years of greatest risk for the development of schizophrenia. Expression of FEZ1, GAD1, and RGS4 showed especially high correlation with one another, in addition to the strongest mean levels of absolute correlation with all other genes studied here. All microarray data are available at NCBI's Gene Expression Omnibus: GEO Series accession number GSE11546 (http://www.ncbi.nlm.nih.gov/geo) [corrected]
复杂神经精神疾病的分子基础很可能涉及许多基因。近年来，已有关于影响精神分裂症及其他神经精神疾病风险的特定基因变异的报道。我们使用定制的DNA微阵列和定量聚合酶链反应（qPCR）来研究假定的精神分裂症易感基因以及正常人脑中相关感兴趣基因的表达。在跨越半个世纪人类衰老过程（18 - 67岁）的72份死后脑样本的前额叶皮质的布罗德曼10区（BA10）中测量了31个基因的表达，这些样本均无神经精神疾病、神经疾病或药物滥用史。对不同年龄阶段的基因表达进行检测，有助于识别那些表达模式与年龄相关的基因，以及那些具有共同表达模式且可能参与与成年早期精神分裂症发生相关的共同细胞机制的基因。在整个研究的年龄范围内，GRM3和RGS4的表达下降，而PRODH和DARPP - 32的表达随年龄增加。NRG1、ERBB3和NGFR在精神分裂症发病风险最高的几年中表现出表达变化。FEZ1、GAD1和RGS4的表达彼此之间具有特别高的相关性，此外与本文研究的所有其他基因的绝对相关性平均水平最强。所有微阵列数据可在NCBI的基因表达综合数据库获取：GEO系列登录号GSE11546（http://www.ncbi.nlm.nih.gov/geo）[已校正]
