Neural Substrates of Anorexia

厌食症的神经基质

• 批准号: 6792614
• 负责人: DAWNA SALTER
• 金额: $ 2.7万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6792614
• 关键词: anorexia; appetite; appetite regulatory center; bioenergetics; body water dehydration; homeostasis; hypothalamus; immunocytochemistry; in situ hybridization; laboratory rat; leptin; neural information processing; neural transmission; neuroanatomy; neuropeptide Y; predoctoral investigator

DESCRIPTION (provided by applicant): The goal of the project is to characterize the organization of central networks involved in anorexia. Anorexia is the loss of appetite, and is a serious complication that increases mortality in a number of human clinical conditions, including AIDS and cancer. Understanding the organization and interactions of circuits involved in generating and reversing anorexia will help us elucidate how these circuits function in both health and disease. Normally a state of negative energy balance elicits mechanisms to increase appetite and food intake. However, in anorexia these compensatory mechanisms fail. To accomplish the goal of this project, three experiments are proposed using a physiological model of anorexia resulting from dehydration (DE). DE-anorexia occurs after drinking hypertonic saline but is robustly reversed within minutes of returning access to drinking water. The experiments are: 1) To determine if DE inhibits eating in response to the orexigen Neuropeptide Y (NPY) when injected into the perifornical area of the lateral hypothalamus or the paraventricular nucleus of the hypothalamus; 2) An analysis of neuronal activation in NPY neurons immediately after anorexia reversal by using imunohistochemical detection of the phosphorylated form of p42/44 mitogen-activated protein/extracellular sinai-regulated kinase (pERK1/2) and in-situ hybridization for NPY mRNA; 3) To determine if low leptin levels are necessary for compensatory feeding after anorexia reversal by providing exogenous leptin to revent the decrease of circulating levels.

描述（由申请人提供）：该项目的目标是描述厌食症中枢网络的组织特征。厌食症是指食欲不振，是一种严重的并发症，会增加许多人类临床疾病（包括艾滋病和癌症）的死亡率。了解产生和逆转厌食症的回路的组织和相互作用将有助于我们阐明这些回路在健康和疾病中如何发挥作用。通常，负能量平衡状态会引发增加食欲和食物摄入的机制。然而，在厌食症中，这些补偿机制会失效。为了实现该项目的目标，提出了三个实验，使用脱水（DE）引起的厌食症生理模型。去厌食症发生在饮用高渗盐水后，但在恢复饮用水后几分钟内即可强劲逆转。实验目的是： 1) 确定当注射到下丘脑外侧孔周区域或下丘脑室旁核时，DE 是否会抑制食欲对食欲素神经肽 Y (NPY) 的反应； 2) 通过免疫组织化学检测 p42/44 丝裂原激活蛋白/细胞外 Sinai 调节激酶 (pERK1/2) 的磷酸化形式和 NPY mRNA 原位杂交，分析厌食逆转后 NPY 神经元的神经元激活情况； 3) 确定低瘦素水平是否是厌食逆转后必要的补偿性喂养，通过提供外源性瘦素来防止循环水平的降低。