Age-related changes in the expression of schizophrenia susceptibility genes in the human prefrontal cortex
Age-related changes in the expression of schizophrenia susceptibility genes in the human prefrontal cortex
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DOI：
10.1007/s00429-008-0181-5
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发表时间：
2008-09-01
影响因子：
3.1
通讯作者：
Kleinman, Joel E.
中科院分区：
文献类型：
--
作者：
Colantuoni, Carlo;Hyde, Thomas M.;Kleinman, Joel E.
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，已经报道了影响精神分裂症和其他神经精神疾病风险的特定遗传变异。我们使用定制的DNA微阵列和qPCR来研究正常人脑中假定的精神分裂症易感基因和相关基因的表达。在跨越半个世纪人类衰老（18-67岁）的72个死后大脑样本的前额叶皮质布罗德曼10区（BA 10）中测量了31个基因的表达，每个样本都没有神经精神疾病、神经系统疾病或药物滥用史。对不同年龄段的表达进行研究，可以鉴定出表达模式与年龄相关的基因，以及共享共同表达模式的基因，这些基因可能参与与成年早期精神分裂症出现相关的共同细胞机制。GRM 3和RGS 4的表达在所调查的整个年龄范围内下降，而PRODH和DARPP-32的表达则随年龄增加。NRG 1、ERBB 3和NGFR在精神分裂症发病风险最高的年份中表现出表达变化。FEZ 1，GAD 1和RGS 4的表达显示出特别高的相互相关性，除了与这里研究的所有其他基因的绝对相关性的最强平均水平。所有微阵列数据可在http://www.ncbi.nlm.nih.gov/geo/（登录号：TBA）获得。
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 http://www.ncbi.nlm.nih.gov/geo/ (accession #: TBA).