发作性睡病（Narcolepsy）是一种具有遗传易感性、受到环境因素影响或触发的疾病。1型发作性睡病是由位于下丘脑hypocretin（或orexin）神经元大量缺失引起。但hypocretin神经元如何凋亡，凋亡后如何引起发作性睡病这些问题尚属未知。本研究通过转基因手段将绿色荧光蛋白和自杀基因转入hypocretin神经元内，构建可活体观察和控制hypocretin神经元凋亡的嗜睡病疾病动物模型；利用该模型研究在发作性睡病患者中发现的突变基因嘌呤受体亚型P2RY11基因和髓磷脂少突胶质细胞糖蛋白MOG基因对hypocretin神经元凋亡的调节作用；利用睡眠觉醒分析系统，差异表达基因分析，神经化学，组织学等手段研究hypocretin神经元凋亡对神经递质，其他中枢神经元以及下游分子的影响。研究结果有助于阐明发作性睡病的致病机制，建立新的临床诊断和治疗方法，为发作性睡病的药物筛选提供新思路。

Narcolepsy is a chronic neurological sleep disorder associated with genetic and environmental factors. Type 1 narcolepsy is caused by extensive loss of hypothalamic neurons that produce the neuropeptides hypocretin(also known as orexin). The pathologic process that destroys the orexin-producing neurons and how the loss of these neurons results in sleepiness are unknown. In this project we will construct a transgenic animal model of narcolepsy whose apoptosis of hypocretin neurons are easily labelled and controllable, study relations of the mutant genes (purine receptor subtypes P2RY11 and myelin oligodendrocytes glycoprotein MOG) found in the patients of narcolepsy with the apoptosis of the hypocretin neurons, research the effect of the apoptosis of the hypocretin neurons on the other types of central neurons, the content of neurotransmitter, and downstream molecular regulation via Sleep/wake behavioral test, analysis of differentially expressed genes, neurochemistry, and histochemistry approaches. The results will provide new strategyies for further understanding narcolepsy, establishing new clinical diagnosis and treatment methods, and drug screening for narcolepsy.