现有研究表明下丘脑食欲素（Hypocretin）在调节HPA轴活性参与抑郁症机制发病中发挥重要作用。申请人研究发现女性抑郁症患者下丘脑外侧区（LHA）Hypocretin-1表达显著高于对照组，人Hypocretin基因组启动子存在类似雌激素受体反应元件，提示雌激素受体可能通过调控Hypocretin的基因表达参与抑郁症发病机制，但相关机制尚未完全阐明。本项目将在死亡后抑郁症患者下丘脑中探究雌激素受体的表达，检测雌激素受体与Hypocretin的共定位情况；其次，在人神经母细胞瘤SK-N-SH中,检测雌激素对内源性Hypocretin的影响；验证雌激素受体调控Hypocretin基因的转录。旨在揭示雌激素对Hypocretin的调控参与抑郁症发病机制，为开发以Hypocretin为靶点的抗抑郁症治疗方案提供科学依据。

Existing studies showed that Hypocretin plays an important role in regulating the activity of HPA axis in the pathogenesis of depression. Our previous studies showed that the Lateral hypothalamic Hypocretin-1 expression was higher in female depression compared with female controls. And There were similar estrogen receptor response component in the Hypocretin genome promoter, which suggested that estrogen receptor may participate in the regulating the gene expression of Hypocretin, which leads to depression, while the relevant mechanism has not been fully elucidated. This project is based on the human brain of depression to investigate the estrogen receptor expression in the hypothalamus and the double labeling of estrogen receptor with Hypocretin-1; and also based on SK-N-SH cells to elucidated the effect of estrogen on endogenous Hypocretin, to verify the transcription of Hypocretin gene by estrogen receptor. The purpose of this study is to reveal the mechanism of the regulation of estrogen to Hypocretin involved in the pathogenesis of depression.We aim to provide the scientific basis for research and development for the application of those antidepressant targeting Hypocretin.