根据基因表达谱与基因功能模块研究大鼠抑郁症发病的分子机制

用Willner法构造大鼠抑郁症模型,由基因芯片检测8例模型和8例正常大鼠的基因表达谱,识别差异表达基因,寻找差异表达基因功能模块并构建基因表达相关网络,研究大鼠抑郁症模型的分子病理机制.在基因本体(GO)功能体系中寻找显著富集差异表达基因的疾病相关功能模块,提取疾病相关功能模块中的基因构造表达相关网络.从中选择显著多地与其它基因共表达的基因定义为HUB基因,并进一步研究其与疾病的关系.筛选得到207个差异表达基因及13个差异表达基因功能模块,主要涉及神经肽激素活性、信号传导通路、核糖体生成以及蛋白质转运与降解.在共表达相关网络中进一步识别了4个差异表达的HUB基因.利用基因功能模块和表达相关网络研究疾病机制的结果显示,抑郁症的发病可能涉及单胺递质的释放、信号传导以及神经肽激素调节等通路协同作用.

Studying molecular mechanisms of depression by a rat model based on gene expression profiles and gene functional modules

Gene expression profiles were measured in 8 Willner disease model rats and 8 untreated control ones for studying the molecular pathology mechanisms of depression.Differentially expressed genes were identified and annotated to Gene Ontology(GO)database to find disease-relevant GO categories significantly enriched with differentially expressed genes,and the co-expression network of genes annotated to the disease-relevant GO categories was constructed to identify differentially expressed HUB genes.207 differentially expressed genes and 13 disease associated GO categories were identified,which are generally related to neuropeptide hormone activity,calmodulin-dependent protein kinase I activity,ribosome biogenesis and protein transport.Furthermore,4 differentially expressed HUB genes of the co-expression network were identified.The results of the analysis based on gene functional modules and co-expression network show that the gene expression alteration of release and signal transduction of monoamine and the neuropeptide hormone activity may be involved in the molecular pathology mechanisms of depression,which indicates that multiple functional modules or pathways may coordinately associate with depression.