FUNCTIONAL NEUROANATOMY OF UROCORTIN IN THE BRAIN

说明(申请人摘要)：促肾上腺皮质激素释放因子(CRF) 被认为是应对压力的主要调节者。最近的克隆和 尿皮质激素(Ucn)是一种CRF样多肽，它的性质开辟了一种新的 CRF多肽家族在大脑中的功能研究方向。 大多数产生UCN的神经元位于Edinger-Westphal核 (EW)，在中脑区发现一些散在的UCN神经元 前脑和脑干区域。UCN的中央管理已显示 表现出强烈的食欲抑制作用。然而，这一机制通过 目前尚不清楚哪些UCN神经元调节食欲。在拟议的项目中， 首先将进行神经解剖学研究以确定潜在的 UCN在大脑中的靶点，并确定UCN神经元的起源 提供了UCN输入。第二，UCN在其目标地区的职能将 被评估。最后，假设内源性UCN神经元参与了 在食欲调节方面将进一步检测UCN基因是否 大脑中的表达可以通过改变代谢条件或通过 重要的外周代谢信号，如瘦素。

DESCRIPTION (applicant's abstract): Corticotropin-releasing factor (CRF) is known to be a major regulator in response to stress. The recent cloning and characterization of urocortin (UCN), a CRF-like peptide, has opened a new direction in the study of the function of the CRF peptide family in the brain. Most of the UCN-producing neurons are found in the Edinger-Westphal nucleus (EW) in the midbrain region, with some scattered UCN neurons found in the forebrain and brainstem regions. Central administration of UCN has been shown to exhibit a potent appetite suppressing effect. However, the mechanism by which UCN neurons modulate appetite is not clear. In the proposed project, neuroanatomical studies will first be performed to determine the potential targets for UCN in the brain and to identify the origin of the UCN neurons that provided the UCN input. Secondly, the function of UCN in its target areas will be assessed. Finally, the hypothesis that endogenous UCN neurons are involved in appetite regulation will be further tested to examine whether UCN gene expression in the brain can be altered by changing metabolic condition or by important peripheral metabolic signals such as leptin.