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Gene expression profiles in rat brain disclose CNS signature genes and regional patterns of functional specialisation

机译:大鼠大脑中的基因表达谱揭示了中枢神经系统的特征基因和功能分型的区域模式

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Background The mammalian brain is divided into distinct regions with structural and neurophysiological differences. As a result, gene expression is likely to vary between regions in relation to their cellular composition and neuronal function. In order to improve our knowledge and understanding of regional patterns of gene expression in the CNS, we have generated a global map of gene expression in selected regions of the adult rat brain (frontomedial-, temporal- and occipital cortex, hippocampus, striatum and cerebellum; both right and left sides) as well as in three major non-neural tissues (spleen, liver and kidney) using the Applied Biosystems Rat Genome Survey Microarray. Results By unsupervised hierarchical clustering, we found that the transcriptome within a region was highly conserved among individual rats and that there were no systematic differences between the two hemispheres (right versus left side). Further, we identified distinct sets of genes showing significant regional enrichment. Functional annotation of each of these gene sets clearly reflected several important physiological features of the region in question, including synaptic transmission within the cortex, neurogenesis in hippocampus and G-protein-mediated signalling in striatum. In addition, we were able to reveal potentially new regional features, such as mRNA transcription- and neurogenesis-annotated activities in cerebellum and differential use of glutamate signalling between regions. Finally, we determined a set of 'CNS-signature' genes that uncover characteristics of several common neuronal processes in the CNS, with marked over-representation of specific features of synaptic transmission, ion transport and cell communication, as well as numerous novel unclassified genes. Conclusion We have generated a global map of gene expression in the rat brain and used this to determine functional processes and pathways that have a regional preference or ubiquitous distribution within the CNS, respectively. The existence of shared specialised neuronal activities in CNS is interesting in a context of potential functional redundancy, and future studies should further explore the overall characteristics of CNS-specific versus region-specific gene profiles in the brain.
机译:背景技术哺乳动物的大脑分为结构和神经生理学差异的不同区域。结果,基因表达可能在区域之间与其细胞组成和神经元功能有关。为了增进我们对中枢神经系统基因表达区域模式的了解和了解,我们在成年大鼠大脑的选定区域(额叶,颞叶和枕叶皮层,海马,纹状体和小脑)生成了全球基因表达图谱;右侧和左侧)以及三个主要的非神经组织(脾脏,肝脏和肾脏)都使用Applied Biosystems大鼠基因组调查微阵列。结果通过无监督的层次聚类,我们发现单个大鼠之间区域内的转录组高度保守,并且两个半球(右侧与左侧)之间没有系统的差异。此外,我们确定了显示显着区域富集的不同基因集。这些基因组的每一个的功能注释清楚地反映了所讨论区域的几个重要生理特征,包括皮质内的突触传递,海马中的神经发生以及纹状体中的G蛋白介导的信号传导。此外,我们能够揭示潜在的新区域特征,例如小脑中的mRNA转录和神经发生注释活动以及区域之间谷氨酸信号的差异使用。最后,我们确定了一组“ CNS签名”基因,这些基因揭示了CNS中几种常见神经元过程的特征,其中突触传递,离子转运和细胞通讯的特定特征的显着过量代表以及许多新的未分类基因。结论我们已经在大鼠大脑中生成了基因表达的全球图谱,并用它来确定在CNS内分别具有区域偏好或普遍分布的功能过程和途径。在潜在的功能冗余的背景下,中枢神经系统中共享的专门神经元活动的存在是令人感兴趣的,并且未来的研究应进一步探索大脑中中枢神经系统特定基因与区域特定基因配置文件的整体特征。

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