Central melanocortin system and MAP-kinase activation

描述（由申请人提供）：黑皮质素系统在调节食物摄入和能量稳态中起关键作用。导致这些激素缺乏或异常表达的基因突变具有肥胖表型。黑皮质素的作用机制以及这些信号如何参与与食物摄入相关的中枢系统仍不清楚。我们实验室的初步数据表明，下丘脑黑皮质素系统参与丝裂原活化蛋白激酶（MAPK）信号转导通路。本申请建议进一步研究这种激活，并将其作为一种工具来研究黑皮质素参与的神经通路。具体地，该提议中的实验被设计为1）检查黑皮质素对MAPK的激活，2）确定黑皮质素处理后具有激活的MAPK的神经元的输入源，3）确定黑皮质素处理后具有激活的MAPK的神经元的神经化学表型，和4）检测由黑皮质素处理引起的基因表达的变化，所述变化可能介导黑皮质素对食物摄取和能量稳态的影响。

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.