ROLE OF GALANIN-EXPRESSING LEPTIN RECEPTOR NEURONS IN LEPTIN ACTION

表达甘丙肽的瘦素受体神经元在瘦素作用中的作用

• 批准号: 8167953
• 负责人: Heike Muenzberg-Gruening
• 金额: $ 23.52万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167953
• 关键词: Ablation; Area; Body Weight; Computer Retrieval of Information on Scientific Projects Database; Eating; Energy Metabolism; Fasting; Feeding behaviors; Funding; Galanin; Goals; Grant; Homeostasis; Institution; Leptin; Mediating; Methods; Mus; Neurons; Obesity; Output; Phenotype; Physiological; Play; Population; Regulation; Reporter; Research; Research Personnel; Resources; Role; Site; Source; Stimulus; System; Tracer; United States National Institutes of Health; gamma-Aminobutyric Acid; leptin receptor; novel

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims We hypothesize that LepRb neurons in the extended perifornical area (exPFA), specifically LepRb(Gal) neurons, play a crucial role in mediating anorexigenic leptin actions via PVN outputs and thus control feeding behavior. Our overall goal is to understand the physiologic function and underlying neuronal network of LepRb(Gal) neurons as well as to investigate the overall population of LepRb neurons in the exPFA. We will thus: 1. Determine the role of LepRb(Gal) neurons in physiologic leptin action. We will examine the phenotype of mice with targeted deletion of LepRb in galanin neurons (LepRbKO(Gal) mice) to determine the contribution of LepRb(Gal) neurons in leptin dependent regulation of energy homeostasis. We will specifically investigate any perturbation in body weight, food intake or energy expenditure in these mice with disrupted LepRb in Galanin neurons. Thus, we expect LepRbKO(Gal) mice to be hyperphagic and obese. 2. Investigate the regulation of LepRb(Gal) neurons. We will use reporter mice to visualize LepRb(Gal) neurons immunohistochemically and define regulatory mechanisms of LepRb(Gal) neurons. We will determine if LepRb or LepRb(Gal) neurons in the exPFA are stimulated by leptin or physiological stimuli like fasting and refeeding (via cFos induction and/or regulation of galanin) and if they co-express the inhibitory transmitter GABA. We will further study the contribution of ARC inputs (e.g. melanocortin system) to regulate LepRb(Gal) neurons by investigating LepRb(Gal) regulation after blockade or ablation of ARC inputs. 3. Investigate the neuroanatomic circuits of LepRb(Gal) neurons. We will define axonal projection sites of LepRb(Gal) neurons (e.g. the PVN) by using traditional and novel tracing methods (LepRb or galanin neuron-specific tracer expression in the exPFA). Furthermore, we will identify the neurons that are innervated by LepRb(Gal) neurons (e.g. in the PVN) or that innervate LepRb(Gal) neurons (e.g. from the ARC), by using LepRb or galanin neuron-specific expression of anterograde or retrograde transsynaptic tracers in the exPFA.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 具体目标 我们假设延伸穹隆周围区(ExPFA)的LepRb神经元，特别是LepRb(Gal)神经元，通过PVN的输出在介导厌食性瘦素活动中发挥关键作用，从而控制摄食行为。我们的总体目标是了解LepRb(Gal)神经元的生理功能和潜在的神经元网络，以及研究ExPFA中LepRb神经元的总体数量。因此，我们会： 1.确定LepRb(Gal)神经元在Leptin生理作用中的作用。我们将研究定向缺失LepRb的甘丙素神经元(LepRbKO(Gal)小鼠)的表型，以确定LepRb(Gal)神经元在瘦素依赖的能量稳态调节中的作用。我们将专门研究这些Galanin神经元LepRb受损的小鼠在体重、食物摄入量或能量消耗方面的任何扰动。因此，我们预计LepRbKO(Gal)小鼠会过度吞噬和肥胖。 2.研究LepRb(Gal)神经元的调控。我们将使用报告小鼠对LepRb(Gal)神经元进行免疫组织化学可视化，并确定LepRb(Gal)神经元的调节机制。我们将确定ExPFA中的LepRb或LepRb(Gal)神经元是否受到瘦素或禁食和再喂养等生理刺激的刺激(通过CFos诱导和/或甘丙素的调节)，以及它们是否共表达抑制性递质GABA。我们将通过研究阻断或消融ARC输入后LepRb(Gal)的调节来进一步研究ARC输入(例如黑素皮质素系统)对LepRb(Gal)神经元的调节作用。 3.研究LepRb(Gal)神经元的神经解剖回路。我们将使用传统和新的追踪方法(ExPFA中的LepRb或Galanin神经元特异性示踪剂表达)来确定LepRb(Gal)神经元(例如PVN)的轴突投射部位。此外，我们将通过在exPFA中使用LepRb或Galanin神经元特异性的顺行或逆行跨突触示踪剂来识别由LepRb(Gal)神经元(例如在PVN中)或LepRb(Gal)神经元(例如来自ARC)支配的神经元。