中枢神经环路对骨代谢的调控机理研究

项目名称： 中枢神经环路对骨代谢的调控机理研究

项目编号： No.81471164

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杨帆

作者单位： 中国科学院深圳先进技术研究院

项目金额： 70万元

中文摘要： 目标：研究下丘脑腹内侧核（VMH）参与调控骨代谢的神经环路机制。下丘脑及其亚核团调控进食等行为的神经环路功能解析近几年获得诸多突破，但下丘脑调控骨代谢的神经环路机制知之甚少。我们以不同特定种类神经元标记的光感基因小鼠为研究对象，用光遗传、神经环路示踪技术，结合电生理、药理遗传学、行为和骨代谢分析等手段，解析VMH脑区局部微环路和参与调控骨代谢的神经环路结构和功能特征。拟研究：1）VMH脑区不同类型的细胞对骨代谢的调控作用；2）参与调解骨代谢的VMH脑区及其神经输入核团与调控焦虑等负面情绪的神经环路结构和功能上的关联特征；3）VMH脑区参与调节骨代谢的神经环路机制；4）长期负面情绪影响骨代谢的生物学和神经环路基础。本研究将：弄清VMH神经环路对骨代谢的调控机理；理解临床上负面情绪与骨质疏松发生相关联的神经表达依据；为理解代谢性疾病发病和干预机理提供新的理论依据，具有重要科学、临床和经济意义。

中文关键词： 下丘脑腹内侧核；骨代谢；光遗传学

英文摘要： Aim: Understanding the mechanism of ventralmedial hypothalamus (VMH) neural circuitry regulating bone metablism. In order to dissect the structural and functional VMH neural circuits in regulating the bone mechanism, we will use the transgenic mice with specific types of neurons labeled with optogenes, combine the techniques of in vivo optogenetic control in free moving mice, viral tracing of neural circuitry, brain slice electrophysiological recordings and real-time bone structural analysis, to study: 1) The effects of regulating specific excitary or inhibitory neurons in VMH to modulate bone metablism; 2) The functional connection between VMH neurons with input neural circuits and its role in regulating bone metablism; 3) The mechanism of regulating neural circuitry in VMH to influence bone metablism; 4) The biological and neural circuitry mechansim of negative emotions (anxiety, depression) influencing the bone metablism. Our study will clarify the mechanism of specific VMH neural circuitry regulating bone metablism, provide fundamental evidence for understanding the neural pathogenesis of metabolic disease such as osteoporosis, and propose a potential strategy to treat the metabolic disease through intervening the hypothalamus activities.

英文关键词： ventral medial hypothalamus;bone metablism;optogenetic