Role of Parabrachial Nucleus Neuropeptides in Feeding

臂旁核神经肽在进食中的作用

• 批准号: 7856882
• 负责人: JOHN-PAUL BAIRD
• 金额: $ 14.13万
• 依托单位: AMHERST COLLEGE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7856882
• 关键词: Accounting; Affect; Agonist; Anorexia; Anosmia; Appetitive Behavior; Attention; Basic Science; Behavioral; Brain; Brain Stem; Bulimia; Cachexia; Cell Nucleus; Cerebral Ventricles; Clinical; Complex; Data Reporting; Diabetes Mellitus; Disease; Dorsal; Dysgeusia; Eating; Failure to Thrive; Feedback; Feeding behaviors; Future; Gastrointestinal tract structure; Gastroparesis; Goals; Health Care Costs; Heart Diseases; Hormones; Hypertension; Hypothalamic structure; Infusion procedures; Injection of therapeutic agent; Insulin; Leptin; Ligands; Link; Location; Mediating; Mediation; Mediator of activation protein; Metabolic Diseases; Metabolism; Movement; Neurons; Neuropeptide Receptor; Neuropeptides; Neurophysiology - biologic function; Nucleus solitarius; Obesity; Oral; Output; Phase; Physiological; Play; Pontine structure; Process; Prosencephalon; Rattus; Reflux; Research; Resolution; Role; SHU 9119; Satiation; Sensory; Signal Transduction; Site; Stimulus; Stomach; Stroke; Structure; Structure of area postrema; System; Taste Perception; Techniques; Testing; Ventricular; Visceral; Visceral Afferents; behavior test; computerized data processing; density; dorsal motor nucleus; feeding; gastrointestinal; ghrelin; hindbrain; insight; melanocortin receptor; melanotan-II; neural circuit; neuropeptide Y; neurophysiology; obesity treatment; orexin A; orexin A receptor; parabrachial nucleus; public health relevance; receptor; relating to nervous system; research study; response; sensory stimulus; therapeutic target

DESCRIPTION (provided by applicant): Advances in obesity treatment may be provided by continued resolution of the neural circuits that mediate leptin, ghrelin, and insulin responses. Considerable recent research has detailed first and second order sites in hypothalamic regions that are sensitive to leptin, insulin, and ghrelin input. Forebrain neurons expressing neuropeptides throughout the brain are sensitive to these hormones and act as downstream mediators to influence feeding and metabolism. These neuropeptides, such as neuropeptide Y (NPY), and orexin-A (ORX), and pro- opioimelanocortin products (MC), act or have receptors in forebrain and hindbrain locations. An important goal for future research is to determine how such neuropeptides function in brainstem nuclei and to determine how these nuclei interact with forebrain nuclei (e.g., hypothalamus) that are sensitive to leptin, ghrelin, and insulin. This proposal will continue to evaluate the effects of NPY, MC, and ORX receptor ligands on feeding and electrophysiological taste and visceral responses in the pontine parabrachial nucleus (PBN), a brainstem nucleus that receives significantly overlapping taste and visceral afferent inputs, receives direct NPY, MC, and ORX input from the hypothalamus, and sends output to brainstem nuclei controlling oral movement. The first experiments assess the effects of direct PBN microinjectons of NPY, MC, and ORX receptor antagonists on feeding microstructure. The following experiments assess the effects of NPY, MC, and ORX receptor antagonists on neural PBN gustatory and gastric distension responses when NPY, MC, and ORX agonists are applied to brain ventricles or their antagonists are microinjected directly around PBN neurons. If direct PBN application of NPY, MC, or ORX receptor ligands affect feeding, this should be observed at the neurophysiological level and will serve to better clarify the functional role(s) of hypothalamic neuropeptides in the brainstem. PUBLIC HEALTH RELEVANCE Feeding and metabolic disorders such as obesity, anorexia, bulimia, failure to thrive, gastric reflux, cachexia, early satiety, delayed gastric emptying, dysgeusia, and anosmia contribute to diseases including hypertension, stroke, diabetes, and heart disease, and they account for many health-care costs. Elucidating the neural systems that control feeding is, therefore, a fundamental goal for clinical as well as basic science. This proposal will continue to explore the role of the brainstem as a site of feeding-related hypothalamic neuropeptide action and thus contribute to basic research that could help to identify potential pharmacological therapeutic targets.

描述（由申请人提供）：肥胖治疗的进展可以通过持续解决介导瘦素，生长素和胰岛素反应的神经回路提供。最近的大量研究详细介绍了下丘脑区域中对瘦素，胰岛素和生长素蛋白输入敏感的一阶和二阶位点。在整个大脑中表达神经肽的前脑神经元对这些激素敏感，并充当下游介体以影响喂养和代谢。这些神经肽，例如神经肽Y（NPY）和OREXIN-A（ORX），以及依非氨基层素的产物（MC），在前脑和后脑位置作用或具有受体或具有受体。未来研究的一个重要目标是确定这种神经肽在脑干核中的作用，并确定这些核与对瘦素，生长素蛋白和胰岛素敏感的前脑核（例如下丘脑）如何相互作用。该提案将继续评估NPY，MC和ORX受体配体对pontine伞兵核（PBN）中喂养和电生理的味道以及内脏反应的影响，该脑干核是一种脑干核，该核是接收到可显着重叠的味觉和脑部npy，MC，Orxi and MC，Orxii and Mc and Orxi and Orxi and Orxii and Orxi and Orx andip and Orx intup的脑部，控制口腔运动。第一个实验评估了NPY，MC和ORX受体拮抗剂对摄食微结构的直接PBN微型注射子的影响。以下实验评估了NPY，MC和ORX受体拮抗剂对NPY，MC和ORX激动剂应用于脑室或其拮抗剂时，将NPY，MC和ORX受体拮抗剂对神经PBN味觉和胃扩张反应的影响直接在PBN神经元附近直接注射。如果直接应用NPY，MC或ORX受体配体会影响喂养，则应在神经生理水平上观察到这一点，并将更好地阐明下丘脑神经肽在脑干中的功能作用。公共卫生相关性喂养和代谢疾病，例如肥胖，厌食症，贪食症，未能成长，胃反流，卡希克西亚，早期饱和度，延迟的胃排空，病毒障碍和厌食症会导致包括高压，疾病，疾病和心脏病等疾病，以及许多疾病，以及许多健康疾病，以及许多疾病。因此，阐明控制喂养的神经系统是临床和基础科学的基本目标。该提案将继续探索脑干作为喂养相关的下丘脑神经肽作用的作用，因此有助于基础研究，这可以帮助鉴定潜在的药理治疗靶标。