Central melanocortin system and MAP-kinase activation

描述(申请人提供)：黑素皮质素系统在调节食物摄入量和能量平衡方面起着关键作用。导致这些激素缺乏或异常表达的基因突变具有肥胖的表型。黑素皮质素的作用机制以及这些信号如何参与与食物摄取相关的中枢系统仍不清楚。我们实验室的初步数据表明，下丘脑黑素皮质素系统参与了丝裂原活化蛋白激酶(MAPK)信号转导途径。这项申请建议进一步研究这种激活，并将其用作研究黑素皮质素参与的神经通路的工具。具体地说，该方案中的实验旨在1)检测黑素皮质素对MAPK的激活，2)确定黑素皮质素治疗后MAPK激活的神经元的输入来源，3)确定黑素皮质素治疗后MAPK激活的神经元的神经化学表型，以及4)检测黑素皮质素治疗引起的基因表达的变化，这些变化可能介导黑素皮质素对食物摄取和能量平衡的影响。

DESCRIPTION (provided by applicant): The melanocortin system plays a key role in the regulation of food intake and energy homeostasis. Genetic mutations that result in the absence of or aberrant expression of these hormones have an obese phenotype. The mechanism of action of melanocortins and how such signals engage central systems related to food intake remain unclear. Preliminary data in our laboratory indicates that the hypothalamic melanocortin system engages the mitogen activated protein kinase (MAPK) signal transduction pathway. This application proposes to further study this activation and to use it as a tool to investigate the neural pathways that are engaged by melanocortins. Specifically, the experiments within this proposal were designed to 1) examine the activation of MAPK by melanocortins, 2) to determine the source of input to neurons with activated MAPK after melanocortin treatment, 3) to determine the neurochemical phenotype of neurons with activated MAPK after melanocortin treatment, and 4) to examine changes in gene expression that result from melanocortin treatment that may mediate the effects of melanocortins on food intake and energy homeostasis.