O'Connor Joann, Muly Emil C, Hemby Scott E
Molecular and Systems Pharmacology Program, Graduate Division of Biological and Behavioral Sciences, Emory University, Atlanta, GA 30322, USA.
Exp Neurol. 2006 Apr;198(2):326-37. doi: 10.1016/j.expneurol.2005.11.028. Epub 2006 Feb 7.
The striatum of the primate brain can be subdivided into three distinct anatomical subregions: caudate (CAU), putamen (PUT), and ventral striatum (VS). Although these subregions share several anatomical connections, cell morphological, and histochemical features, they differ considerably in their vulnerability to different neurological and psychiatric diseases, and these brain regions have significantly different functions in health and disease. In order to better understand the molecular underpinnings of the different disease and functional vulnerabilities, transcriptional profiles were generated from the CAU, PUT, and VS of five juvenile rhesus macaques (Macaca mulatta) using human cDNA neuromicroarrays containing triplicate spots of 1227 cDNAs. Differences in microarray gene expression were assessed using z score analysis and 1.5-fold change between paired subregions. Clustering of genes based on dissimilarity of expression patterns between regions revealed subregion specific expression profiles encoding G-protein-coupled receptor signaling transcripts, transcription factors, kinases and phosphatases, and cell signaling and signal transduction transcripts. Twelve transcripts were examined using quantitative real-time PCR (qPCR), and 81% demonstrated alterations similar to those seen with microarray analysis, some of which were statistically significant. Subregion specific transcription profiles support the anatomical differentiation and potential disease vulnerabilities of the respective subregions.
尾状核(CAU)、壳核(PUT)和腹侧纹状体(VS)。尽管这些亚区域共享一些解剖学连接、细胞形态学和组织化学特征,但它们对不同神经和精神疾病的易感性差异很大,并且这些脑区在健康和疾病状态下具有显著不同的功能。为了更好地理解不同疾病和功能易感性的分子基础,我们使用包含1227个cDNA重复点的人类cDNA神经微阵列,从五只幼年恒河猴(猕猴)的CAU、PUT和VS中生成了转录谱。使用z评分分析和配对亚区域之间1.5倍的变化来评估微阵列基因表达的差异。基于区域间表达模式差异对基因进行聚类,揭示了编码G蛋白偶联受体信号转录本、转录因子、激酶和磷酸酶以及细胞信号和信号转导转录本的亚区域特异性表达谱。使用定量实时PCR(qPCR)检测了12个转录本,其中81%表现出与微阵列分析相似的变化,其中一些具有统计学意义。亚区域特异性转录谱支持了各个亚区域的解剖学分化和潜在疾病易感性。