Neural Substrates of Anorexia

描述（由申请人提供）：该项目的目标是描述厌食症涉及的中央网络的组织特征。厌食症是食欲不振，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。了解参与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的功能。通常情况下，负能量平衡的状态会激发增加食欲和食物摄入的机制。然而，在厌食症中，这些补偿机制失败了。为了完成这个项目的目标，提出了三个实验，使用生理模型的厌食症导致脱水（DE）。DE-厌食症发生在饮用高渗盐水后，但在恢复饮用水的几分钟内强烈逆转。实验是：1）确定当将DE注射到外侧下丘脑的穹窿周围区或下丘脑室旁核时，DE是否响应于食欲素神经肽Y（NPY）而抑制进食; 2）通过使用磷酸化形式的p42/44丝裂原活化蛋白/细胞外sinai-regulated kinase（pERK 1/2）的免疫组织化学检测，分析厌食症逆转后立即在NPY神经元中的神经元活化。3）通过外源性瘦素（leptin）逆转厌食症大鼠循环中瘦素水平的下降，以确定低水平的leptin是否是厌食症逆转后代偿性进食的必要条件。

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.