Role of Parabrachial Nucleus Neuropeptides in Feeding

臂旁核神经肽在进食中的作用

• 批准号: 6898084
• 负责人: JOHN-PAUL BAIRD
• 金额: $ 22.08万
• 依托单位: AMHERST COLLEGE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6898084
• 关键词: behavior test; eating; electrophysiology; inhibitor /antagonist; laboratory rat; microinjections; neuropeptides; neurophysiology; parabrachial nucleus; protein structure function; taste

DESCRIPTION (provided by applicant): 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 account for many health-care costs. Elucidating the neural systems that control feeding is a fundamental goal for clinical as well as basic science. Studies have identified brain areas that are sensitive to hormones that affect feeding and adiposity: leptin, ghrelin, and insulin. Scientists have identified neuropeptides in the brain that are sensitive to these hormones and act as downstream mediators to influence feeding and metabolism. These neuropeptides, such as neuropeptide Y (NPY), and melanin-concentrating hormone (MCH), 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 evaluate the effects of MCH and NPY 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 and MCH input from the hypothalamus, and sends output to brainstem nuclei controlling oral movement. The first experiments assess effects of direct PBN microinjectons of MCH and NPY and respective antagonists on feeding microstructure. Following experiments assess the effects of MCH and NPY on neural PBN gustatory and gastric distension responses when MCH and NPY and respective antagonists are applied to brain ventricles or microinjected directly around PBN neurons. If direct PBN application of MCH or NPY affects 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.

描述（由申请人提供）：喂养和代谢紊乱，如肥胖、厌食症、暴食症、发育不良、胃反流、恶病质、早饱、胃排空延迟、嗅觉障碍和嗅觉缺失，会导致高血压、中风、糖尿病和心脏病等疾病，并导致许多医疗保健费用。阐明控制进食的神经系统是临床和基础科学的基本目标。研究已经确定了对影响进食和肥胖的激素敏感的大脑区域：瘦素、胃饥饿素和胰岛素。科学家们已经确定了大脑中对这些激素敏感的神经肽，并作为下游介质影响摄食和新陈代谢。这些神经肽，如神经肽Y （NPY）和黑色素浓缩激素（MCH），在前脑和后脑的位置起作用或具有受体。未来研究的一个重要目标是确定这些神经肽如何在脑干核中起作用，并确定这些核如何与对瘦素、胃饥饿素和胰岛素敏感的前脑核（如下丘脑）相互作用。本研究将评估MCH和NPY对脑干脑桥臂旁核（PBN）进食和电生理味觉和内脏反应的影响。PBN是一个脑干核，接收明显重叠的味觉和内脏传入输入，直接接收来自下丘脑的NPY和MCH输入，并将输出发送到控制口腔运动的脑干核。第一个实验评估了直接注射PBN微注射MCH和NPY及其拮抗剂对饲养微观结构的影响。接下来的实验评估了MCH和NPY及其拮抗剂分别应用于脑室或直接在PBN神经元周围微注射时，MCH和NPY对神经PBN味觉和胃扩张反应的影响。如果直接使用PBN的MCH或NPY会影响进食，这应该在神经生理学水平上观察，并将有助于更好地阐明下丘脑神经肽在脑干中的功能作用。