下丘脑腹内侧核CRH信号调控葡萄糖代谢的机制

应激产生的高血糖是机体应对生存威胁的一种适应方式，然而长期的应激会导致葡萄糖代谢的紊乱。促肾上腺激素释放激素（CRH），作为应激反应的最重要激素之一，可能直接参与了葡萄糖代谢的调控。在此立项项目中，申请人提出如下假设：下丘脑室旁核的CRH神经元投射至腹内侧核（VMH）区域并通过CRH的两类受体（CRHR1、CRHR2）来调节能量代谢的平衡。申请人将通过神经元示踪的方法重构下丘脑室旁核CRH神经元对VMH区域的投射，并利用在体钙成像技术观察两类CRH受体神经元对急性和慢性应激中葡萄糖调控的参与程度，利用电生理手段来研究CRH对VMH神经元活性的影响及胞内的分子信号通路。申请人将从分子、突触、神经环路及行为学等多水平来研究应激与能量代谢的关系，从而为临床上精神类疾病和代谢紊乱的并发症提供一定的理论基础。

Stress-induced hyperglycemia provides a quickly accessible energy supply when facing significant threats, thereby promoting an individual’s survival. Corticotropin releasing hormone (CRH), the central driver for HPA-axis in response to stress, might be involved in the regulation of glucose metabolism. Here, we hypothesize that the ventromedial hypothalamic (VMH) CRH may regulate energy homeostasis by acting on different CRH receptors during stress response. We aim to map the CRH-VMH neural circuit, to investigate CRH effect on glucose metabolism in the VMH during stress response and the intracellular molecular pathway during CRH receptor activation. Thus, the present proposal focus on the study of stress induced hyperglycemia from synaptic level, molecular level, neural circuit level and behavior level, which may shed the light on the interaction between stress response and energy metabolism.