Neural Substrates of Anorexia

描述(由申请人提供)：该项目的目标是描述与厌食症有关的中央网络的组织结构。厌食症是食欲不振，是一种严重的并发症，在包括艾滋病和癌症在内的许多人类临床疾病中会增加死亡率。了解参与厌食症发生和逆转的回路的组织和相互作用将有助于我们阐明这些回路如何在健康和疾病中发挥作用。正常情况下，负能量平衡状态会引发增加食欲和食物摄入量的机制。然而，在厌食症中，这些补偿机制失效了。为了实现这个项目的目标，提出了三个实验，使用脱水引起的厌食症(DE)的生理模型。反厌食症在饮用高渗盐水后发生，但在重新获得饮用水后几分钟内就会强劲逆转。实验包括：1)确定DE注射到下丘脑外侧穹隆周围区或下丘脑室旁核是否能抑制Orexigen神经肽Y(NPY)对进食的反应；2)通过提供外源性瘦素来分析厌食逆转后NPY神经元的激活情况，方法是通过对p42/44丝裂原活化蛋白/细胞外Sinai调节激酶(pERK1/2)磷酸化形式的免疫组织化学检测和NPY mRNA的原位杂交，来确定厌食逆转后是否需要低水平的瘦素来进行代偿喂养。

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.