雌激素对女性神经性厌食5-HT通路相关基因的DNA甲基化调控研究

项目名称： 雌激素对女性神经性厌食5-HT通路相关基因的DNA甲基化调控研究

项目编号： No.81201055

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 陈珏

作者单位： 上海市精神卫生中心

项目金额： 23万元

中文摘要： 神经性厌食（AN）是我国近年来快速增长、年轻女性多发的慢性难治性精神障碍。目前普遍认为5-HT能低下是AN的病因之一，但单用提高5-HT的药物疗效不佳。申请人前期初步证明女性AN患者5-HT水平低下的同时雌激素水平普遍低下，而恢复中的AN患者5-HT水平和雌激素水平均有升高。生物学研究发现脑神经甾体激素- - 雌激素对脑内5-HT具调节作用。本研究拟以首发未治疗的女性AN患者为研究对象，采用同期健康对照，及以雌激素为干预的前瞻性随机对照研究，观察雌激素治疗组和非雌激素治疗组治疗前后临床症状变化，以及5-HT通路相关基因DNA甲基化、mRNA表达及5-HT水平三个层面变化特点和其间的关联，以验证研究假设- - 雌激素可通过影响AN患者5-HT通路相关基因的DNA甲基化水平、最终提高中枢5-HT能而改善AN核心症状；在进一步阐明AN的神经病理机制同时，为AN的潜在治疗方法- - 雌激素治疗法提供理论依据。

中文关键词： 神经性厌食；5-HT；雌激素；DNA甲基化；

英文摘要： Anorexia Nervosa (AN) is a chronic refractory mental disorder commonly occurring among young females with high mortality. Its morbidity in China has been increasing rapidly in recent years. It's commonly held that low level of 5-HT is one of the pathogenic factors of AN. However, single usage of 5-HT increasing drugs showed limited effect. Our rudimentary research found that low level of 5-HT was universally accompanied with low level of estrogen among female AN patients, and both 5-HT and estrogen level increased among recovering AN patients. Biological studies found that estrogen, which is a neurosteroid hormone in the brain, showed regulating effect on 5-HT level in the brain. In the current study, we recruit first onset drug na?ve female patients with AN and healthy subjects, adopting a prospective randomized control method to observe the clinical symptoms change before and after treatment among estrogen intervention group and intervention free group. We also investigate the DNA methylation, mRNA expression of the genes related to 5-HT circuit, 5-HT level change and their interrelations. We hypothesize that low level of estrogen is one of the underlying pathophysiological mechanisms resulting the chronic process of AN. We postulate estrogen can increase central 5-HT level through its effect on DNA methylatio

英文关键词： anorexia nervosa；5-HT；estrogen；DNA Methylation；