Department of Gene and Protein Biomarkers, GenProMarkers Inc., Rockville, MD 20850, USA.
Int J Biol Sci. 2011 Mar 29;7(3):308-22. doi: 10.7150/ijbs.7.308.
Mitochondrial function is of particular importance in brain because of its high demand for energy (ATP) and efficient removal of reactive oxygen species (ROS). We developed rat mitochondrion-neuron focused microarray (rMNChip) and integrated bioinformatics tools for rapid identification of differential pathways in brain tissues. rMNChip contains 1,500 genes involved in mitochondrial functions, stress response, circadian rhythms and signal transduction. The bioinformatics tool includes an algorithm for computing of differentially expressed genes, and a database for straightforward and intuitive interpretation for microarray results. Our application of these tools to RNA samples derived from rat frontal cortex (FC), hippocampus (HC) and hypothalamus (HT) led to the identification of differentially-expressed signal-transduction-bioenergenesis and neurotransmitter-synthesis pathways with a dominant number of genes (FC/HC = 55/6; FC/HT = 55/4) having significantly (p<0.05, FDR<10.70%) higher (≥1.25 fold) RNA levels in the frontal cortex than the others, strongly suggesting active generation of ATP and neurotransmitters and efficient removal of ROS. Thus, these tools for rapid and efficient identification of differential pathways in brain regions will greatly facilitate our systems-biological study and understanding of molecular mechanisms underlying complex and multifactorial neurodegenerative diseases.
线粒体功能在大脑中尤为重要，因为大脑对能量（ATP）的需求很高，并且需要有效清除活性氧（ROS）。我们开发了大鼠线粒体-神经元聚焦微阵列（rMNChip）和集成的生物信息学工具，用于快速识别脑组织中的差异途径。rMNChip 包含 1500 个与线粒体功能、应激反应、昼夜节律和信号转导相关的基因。生物信息学工具包括一种用于计算差异表达基因的算法，以及一个用于直观解释微阵列结果的数据库。我们将这些工具应用于源自大鼠前额叶皮层（FC）、海马体（HC）和下丘脑（HT）的 RNA 样本，鉴定出差异表达的信号转导-生物能和神经递质合成途径，其中具有大量基因（FC/HC = 55/6；FC/HT = 55/4）的信号转导-生物能和神经递质合成途径的 RNA 水平显著升高（p<0.05，FDR<10.70%），明显高于其他途径，强烈提示活跃的 ATP 和神经递质生成以及 ROS 的有效清除。因此，这些用于快速高效识别大脑区域差异途径的工具将极大地促进我们对复杂多因素神经退行性疾病的分子机制的系统生物学研究和理解。
