ROLE OF BRAINSTEM CRH IN INTAKE AND BODY WEIGHT CONTROL

脑干 CRH 在摄入量和体重控制中的作用

• 批准号: 6340231
• 负责人: STACY M ROTH
• 金额: $ 2.37万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-07 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6340231
• 关键词: adrenocorticotropic hormone; blood glucose; body weight; brain stem; corticosterone; corticotropin releasing factor; decerebration; epinephrine; free fatty acids; gene induction /repression; glucagon; hormone receptor; hormone regulation /control mechanism; hyperglycemia; immunocytochemistry; insulin; laboratory rat; milk; neurogenetics; norepinephrine; nutrient intake activity; prosencephalon; protooncogene; psychopharmacology; weight control

An appreciation of the actions and interactions of a number of neuropeptides is essential for the development of effective pharmacological approaches to feeding disorders and obesity. Mounting evidence suggests that the corticotropin releasing hormone (CRH) system, best known for its role in stress reactions, is an important contributor to feeding and body weight control under normal conditions. The problem addressed in the proposal concerns the central location of the CRH receptors relevant to energy homeostasis. Researchers have tended to focus almost exclusively on hypothalamic structures, despite the fact that CRH neurons and receptors are widely distributed. The proposed experiments evaluate functional contributions of CRH receptors within the caudal brainstem. Urocortin, a CRH agonist, will be delivered to the lateral (forebrain) and fourth (brainstem) ventricles, and to two structures (dorsal vagal complex and parabrachial nucleus) in the brainstem. We will evaluate treatment effects: (1) on short- and long- term intake and body weight, (2) on a set of blood plasma parameters relevant to energy homeostasis including metabolic fuels (glucose, free fatty acids), hormones controlling energy storage and utilization (insulin, glucagon), and correlates of activity in the hypothalamo-pituitary axis (ACTH, corticosterone) and the sympathetic nervous system (epinephrine, norepinephrine), (3) Fos-like immunoreactivity and (4) in chronic decerebrate rats in which neural connections between hypothalamic and brainstem components of the CRH system have been eliminated.

对许多神经肽的作用和相互作用的欣赏对于开发有效的药理学方法至关重要。越来越多的证据表明，以其在压力反应中的作用而闻名的皮质激素释放激素（CRH）系统是正常条件下喂养和体重控制的重要贡献。该提案中解决的问题涉及与能量稳态相关的CRH受体的中心位置。尽管CRH神经元和受体分布广泛，但研究人员倾向于几乎专注于下丘脑结构。提出的实验评估了尾脑干内CRH受体的功能贡献。泌尿科素，一种CRH激动剂，将递送到脑干中的横向（前脑）和第四（脑干）心室，以及两个结构（背部迷走神经复合物和副核）。 We will evaluate treatment effects: (1) on short- and long- term intake and body weight, (2) on a set of blood plasma parameters relevant to energy homeostasis including metabolic fuels (glucose, free fatty acids), hormones controlling energy storage and utilization (insulin, glucagon), and correlates of activity in the hypothalamo-pituitary axis (ACTH, corticosterone) and the sympathetic神经系统（肾上腺素，去甲肾上腺素），（3）在慢性杂交大鼠中类似FOS样的免疫反应性和（4），其中消除了下丘脑和脑干组成部分之间的神经连接。