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）：该项目的目的是表征涉及厌食症的中央网络的组织。厌食症是食欲不振，是一种严重的并发症，在许多人类临床状况（包括艾滋病和癌症）中增加了死亡率。了解与产生和逆转厌食症有关的电路的组织和相互作用将有助于我们阐明这些电路在健康和疾病中的作用。通常，一种负能量平衡状态会引起增加食欲和食物摄入量的机制。但是，在厌食中，这些补偿机制失败了。为了实现该项目的目标，使用脱水（DE）引起的厌食症的生理模型提出了三个实验。在喝高渗盐水后发生的抗震颤发生，但在返回饮用水后几分钟内就会有力逆转。实验是：1）确定DE是否会抑制对甲状腺肿的神经肽Y（NPY）的响应，当注射到下丘脑外侧下丘脑或下丘脑的旁腔核核时； 2）通过使用p42/44丝裂原激活蛋白/细胞外调节的激酶（PERK1/2）的磷酸化形式（PERK1/2）和npy果实化的磷酸化形式的磷酸化形式和npy果实来分析NPY神经元逆转后NPY神经元的神经元激活。 3）通过提供外源瘦素以使循环水平的降低来确定厌食症逆转后补偿性喂养是否需要低瘦素水平。