Abstract

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.

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