Role of NTS POMC neurons in energy homeostasis

NTS POMC 神经元在能量稳态中的作用

• 批准号: 7495288
• 负责人: Suzanne M Appleyard
• 金额: $ 6.51万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-15 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7495288
• 关键词: Ablation; Address; Affect; Appetite Regulation; Area; Body Weight; Brain; Brain Stem; Brain region; Cardiovascular Diseases; Catecholamines; Cells; Child; Cholecystokinin; Data; Diabetes Mellitus; Diphtheria Toxin; Eating; FOS gene; Foundations; Goals; Health; Homeostasis; Hormonal; Hypothalamic structure; Intervention; Investigation; Ions; Knowledge; Label; Laboratories; Leptin; Life; Metabolism; Molecular; Mus; Mutation; Neural Pathways; Neuromodulator; Neurons; Neurotransmitters; Nucleus solitarius; Obesity; Opioid; Pathway interactions; Peptides; Pharmaceutical Preparations; Pharmacotherapy; Play; Preparation; Pro-Opiomelanocortin; Property; Receptor Gene; Regulation; Research; Research Personnel; Role; Satiation; Sensory; Severities; Signal Transduction; Site; Slice; Structure of nucleus infundibularis hypothalami; Synapses; System; Techniques; Testing; Training; Transgenic Mice; Visceral; career; early onset; energy balance; experience; feeding; gamma-Aminobutyric Acid; glucagon-like peptide 1; neurochemistry; neuronal cell body; sensor

Obesity is a major health problem in the Western wodd and is a leading contributor to cardiovascular disease and diabetes mellitus. The causes of obesity are multifactorial. However, its severity and early onset in children with monogenic mutations in the proopiomelanocortin (POMC) and metanocortin-4 receptor genes highlight the importance of the POMC system in the regulation of energy balance. Remarkably, the cell bodies of POMC neurons are located in only two regions of the brain: the arcuate nucleus of the hypothalamus (ARC) and the nucleus of the solitary tract (NTS) in the medulla. As any pharmacological intervention using either melanocortin or opioid drugs will affect the signaling from both regions, it is critical to determine the function of the NTS-POMC neurons for rational predictions concerning the long-term consequences of drug therapy aimed at these targets. However, although the NTS receives visceral sensory inputs and is interconnected with regions proposed to act as feeding centers, the role of the POMC neurons in the NTS in energy homeostasis remains unknown. I hypothesize that these NTS-POMC neurons are a vital component of neural pathways that control energy homeostasis and are capable of integrating the sensory afferent and hormonal input into the NTS. This research plan uses a multi-disciplinary approach to address key aspects of this hypothesis. The Low lab has recently developed transgenic mice in which the POMC neurons are identified by EGFP, allowing the examination of the rote of these POMC neurons in the NTS pathways, using both electrophysiologicat and immunocytochemical techniques The proposed specific aims wilt identify neuroanatomic, neurochemical, regulatory, and molecular properties of NTS-POMC neurons, tn addition, I plan to ablate the NTS-POMC neurons to directly determine if they are important for energy balance. An important aspect of this proposal are the training goals. Dr. Michael Andresen's knowledge and experience with his unique set up for studying NTS neurons and their regulation by afferent inputs are critical for this proposal to characterize the NTS POMC neurons using electrophysiological approaches. Additionally, 1plan to expand my training in immunocytochemicat and retrotabeting studies by utilizing the extensive experience and knowledge in this area available at OHSU, as these techniques will be invaluable for my long-term career goal of becoming an independent investigator.

肥胖是西方世界的一个主要健康问题，是心血管疾病的主要诱因。 疾病和糖尿病。肥胖的原因是多方面的。然而，其严重性和早期 阿黑皮素原（POMC）和后皮质素-4受体单基因突变的儿童发病 基因的研究突出了POMC系统在能量平衡调节中的重要性。值得注意的是， POMC神经元的细胞体仅位于脑的两个区域： 下丘脑（ARC）和延髓中的孤束核（NTS）。作为任何药理学 使用黑皮质素或阿片类药物的干预将影响来自两个区域的信号，这是至关重要的 确定NTS-POMC神经元的功能，以合理预测长期 针对这些目标的药物治疗的后果。然而，尽管NTS接收内脏 感觉输入，并与建议作为摄食中心的区域相互联系，POMC的作用 NTS中的神经元在能量稳态中的作用仍然未知。我假设这些NTS-POMC神经元 是控制能量稳态的神经通路的重要组成部分，并能够整合 感觉传入和激素输入到NTS。本研究计划采用多学科方法， 解决这个假设的关键方面。Low实验室最近开发了转基因小鼠， 通过EGFP鉴定POMC神经元，允许检查这些POMC神经元在细胞中的位置。 使用电生理学和免疫细胞化学技术研究NTS途径 目的将确定NTS-POMC的神经解剖学，神经化学，调节和分子特性 此外，我计划消融NTS-POMC神经元，以直接确定它们是否对 能量平衡这项建议的一个重要方面是培训目标。迈克尔·安德森博士 知识和经验，他独特的设置，研究NTS神经元和他们的调节传入 输入对于该提议使用电生理学来表征NTS POMC神经元是至关重要的 接近。此外，我计划通过以下方式扩大我在免疫细胞化学和retrotabeting研究方面的培训： 利用OHSU在这一领域的丰富经验和知识，因为这些技术将 这对我成为一名独立调查员的长期职业目标来说是无价的。