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

描述（由申请人提供）：食物摄入受许多大脑结构，特别是下丘脑内的调节。下丘脑的一个结构，背内侧核（DMN），被认为是调节食物摄入的。最近在鸟类中发现的一种神经肽，促性腺激素抑制激素（GnIH），可以抑制繁殖并刺激食物摄入。在哺乳动物中，DMN中描述了一种相关的神经肽，并确定为GnIH-3。GnIH-3对增加大鼠食物摄入量有较强的作用。GnIH-3对食物摄入影响的神经机制几乎没有得到关注。在大鼠中，GnIH-3中枢治疗增加下丘脑神经肽Y （NPY）和生长激素释放激素mrna。已知NPY增加会刺激食物摄入。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是否会刺激其他调节食物摄入的下丘脑神经肽。因此，本应用的目的首先是确定GnIH-3下游靶点神经元的表型。其次，本应用试图通过推断NPY神经元是否共同表达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，本研究将确定GnIH-3诱导的GH释放与下丘脑NPY mRNA增加之间的因果关系。因此，这项应用的创新之处在于，它试图了解GnIH-3在DMN中调节食物摄入的鲜为人知的作用。GnIH-3对食物摄入的影响在每一个被研究的物种中都有描述，但调节这种影响的神经回路尚未被研究过。更广泛的应用范围在于对本科生的培养。提出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。这种技术的结合向受训者展示了神经科学的跨学科方面，并帮助他们为学士学位后的教育做好准备。此外，霍普学院的使命是“通过实践研究来教学”，这让我的学生有机会在实验室里进行研究，写科学论文，并在国家会议上展示数据。学生甚至有机会做少量的教学，如果愿意的话。在过去的7年里，我实验室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.