抑郁症治疗的新靶点 - - 甘丙肽及其受体对单胺能上行投射系统的调控

项目名称： 抑郁症治疗的新靶点 - - 甘丙肽及其受体对单胺能上行投射系统的调控

项目编号： No.30870815

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 徐志卿

作者单位： 首都医科大学

项目金额： 35万元

中文摘要： 本项目以抑郁症为研究对象，从整体、细胞和分子水平，以甘丙肽及其受体亚型为突破口，深入研究神经肽在抑郁症发病和治疗中的作用机制，分析了相关甘丙肽受体亚型在5-HT和NA上行投射系统的分布变化及其在抑郁症发生和治疗过程中的作用；探讨了甘丙肽及其受体对5-HT和NA系统调控的机制；分析了甘丙肽受体亚型及信号转导通路与抑郁发生和治疗的相关性，并结合临床对甘丙肽及其受体在抑郁症发病和治疗中的作用及机制进行了探讨，初步筛选出与抑郁发生和治疗高度相关的信号转导通路的可能靶点分子，为抑郁症的治疗提供了新的靶点和思路。

中文关键词： 甘丙肽；抑郁症；五羟色胺；去甲肾上腺素

英文摘要： Major depression is a serious disease that will affect 3% of human in the world during their lifetime. Thus a huge number of human beings, and their relatives suffer, and the costs for society are correspondingly large. In the present study the functional significance of neuropeptides galanin in mechanisms underlying mood control was studied by analyzing the role of galanin and its receptors, and their interaction with classic transmitters in two important brain areas, the noradrenergic locus coeruleus and the serotonergic dorsal raphe nucleus. To link the potential role of galanin to the patophysiology of depression, behavioural studies will be performed in depression models of trauma and stress. The galaninergic receptor mechanisms in modulation of the activity of the ascending 5-HT and NA neurons were analysed with several methodologies, including histochemistry, electrophysiology, pharmacology, biophysiology, molecular biology and behavioral approaches. The difference of expression level of galanin in blood from normal and depressed patiens was investigated. Our findings indicate an involvement of galaninergic mechanisms in depression and may lead to development of therapeutic molecules and devices for treatment of major depression.

英文关键词： Neuropeptide; 5-HT; NA; signaling; targets