To Feed or Breed? GnIH-3 Stimulates Food Intake in Rats

描述(申请人提供)：食物摄入量由许多大脑结构调节，特别是在下丘脑。众所周知，下丘脑的一个结构是背内侧核(DMN)，它负责调节食物的摄入量。最近在鸟类中发现的一种神经肽，促性腺激素抑制激素(GnIH)，可以抑制生殖和刺激食物摄取。在哺乳动物中，DMN中已经描述了一种相关的神经肽，并被鉴定为GnIH-3。GnIH-3具有明显的增加大鼠摄食量的作用。GnIH-3‘S影响摄食量的神经机制几乎没有受到关注。在大鼠中，中枢治疗GnIH-3增加了下丘脑神经肽Y(NPY)和生长激素释放激素mRNAs。众所周知，NPY的增加会刺激食物的摄取。然而，目前尚不清楚GnIH-3是直接增加NPY，还是通过增加循环生长激素(GH)水平来增加NPY；也不知道GnIH-3是否刺激其他调节食物摄入的下丘脑神经肽。因此，这项应用的目标是首先确定作为GnIH-3下游靶点的神经元的表型。其次，这项应用试图通过推断NPY神经元是否共表达GnIH-3受体来确定GnIH-3是否具有直接作用于NPY神经元的潜力。第三，这项研究将确定GnIH-3诱导的GH释放和下丘脑NPY mRNA增加之间的因果联系。因此，这一应用的创新之处在于，它试图了解GnIH-3在DMN中调节食物摄入量的鲜为人知的角色。GnIH-3的S效应在每一种被研究的物种中都有描述，但调节这种效应的神经回路到目前为止还没有被研究过。这一应用的更广泛范围在于对本科生的培养。拟议的实验结合了行为学、外科、组织学、解剖学和分子生物学技术。这种技术的结合向学员展示了神经科学的跨学科方面，并帮助他们为毕业后的教育做好准备。此外，希望学院的使命是“通过实践研究进行教学”，这使我的学生有机会进入实验室，进行研究，撰写科学论文，并在全国会议上提交数据。如果愿意，学生甚至有机会进行少量的教学。在过去的7年里，我的实验室里的大多数学生都是女性和/或来自代表性不足的群体。

DESCRIPTION (provided by applicant): Food intake is regulated by numerous brain structures, particularly within the hypothalamus. One hypothalamic structure, the dorsomedial nucleus (DMN), is known to regulate food intake. A recently described neuropeptide in birds, gonadotropin inhibitory hormone (GnIH), inhibits reproduction and stimulates food intake. In mammals, a related neuropeptide has been described in the DMN and identified as GnIH-3. GnIH-3 shows a strong effect to increase food intake in rats. Little to no attention has been given to the neural mechanisms underlying GnIH-3's effects on food intake. In rats, central treatment of GnIH-3 increases hypothalamic neuropeptide Y (NPY) and growth hormone releasing hormone mRNAs. Increased NPY is known to stimulate food intake. It is not known, however, if GnIH-3 increases NPY directly or if it increases NPY via increased levels of circulating growth hormone (GH); nor is it known if GnIH-3 stimulates other hypothalamic neuropeptides that regulate food intake. Thus the objectives of this application are first to determine the phenotype of neurons that are downstream targets of GnIH-3. Second, this application seeks to determine if GnIH-3 has the potential to act directly upon NPY neurons by deducing if NPY neurons co-express the GnIH-3 receptor. Third, this study will determine a causal link between GnIH-3- induced GH release and the increase in hypothalamic NPY mRNA. Thus the innovation of this application is that it seeks to understand the poorly understood role of GnIH-3 within the DMN to regulate food intake. GnIH-3's effects on food intake are described in every species examined, but the neural circuitry that modulates this effect has, as yet, not been investigated. The broader scope of this application lies in the training of undergraduate students. The proposed experiments combine behavioral, surgical, histological, anatomical, and molecular biological techniques. This combination of techniques illustrates to trainees the interdisciplinary aspects to neuroscience and helps prepare them for post-baccalaureate education. Furthermore, Hope College's mission towards "Teaching Through Hands-on Research" gives my students an opportunity to be in the laboratory, to perform research, to write scientific papers and to present data at national meetings. Students even have the opportunity to do a small amount of teaching if desired. The majority of students in my laboratory over the last 7 years have been women and/or from under-represented groups.