INTERACTIONS OF LEPTIN AND CENTRAL SEROTONIN SYSTEMS

描述：（改编自研究者摘要）在美国 今天，异常的食物摄入和体重调节是普遍的， 表现为极端的肥胖和神经性厌食症。中央 神经系统严格控制食物摄入和体重。中央电路 利用5-羟色胺（5-HT）发挥强大的行为效应， 体重然而，5-羟色胺在调节 喂养和体重不清楚。最近的研究表明， 瘦素作为能量平衡和神经内分泌调节的基础 功能瘦素和β-肾上腺素能激动剂的给药抑制食物 摄入然而，尚不清楚瘦素和血清素系统是否在体内相互作用。 CNS。我们的初步研究结果表明，瘦素参与了β-肾上腺素能 中缝背核的神经元。我们假设， 摄食上的瘦素能系统收敛于瘦素调节系统作为最终的 共同的输出机制，并将在我们的具体目标测试这些想法。我们将 还将这些知识扩展到人类大脑， 关于调节食物摄入的机制的信息 在肥胖症和饮食失调如神经性厌食症中异常。在这 建议，我们概述了旨在表征神经解剖学的实验， 瘦素和血清素系统相互作用调节食物的机制 摄入首先，我们将确定和表征的化学身份 表达5-HT 2C和5-HT 1B受体的下丘脑神经元， 受体被认为调节食物摄取和体重。我们将使用dual 5-HT 2C和5-HT 1B mRNA标记原位杂交与ISHH偶联， 已知调节食物摄入的神经肽。接下来，使用逆行追踪， 5-HT 2C和5-HT 1B受体mRNA的原位杂交，我们将确定是否 支配关键自主调节部位的下丘脑神经元接受 能神经支配，表达5-HT 1B和2C受体mRNA。三是利用 逆行追踪和原位杂交即刻早期基因，我们将 确定中枢神经系统的网站由瘦素反应神经元在背 中缝核最后，使用逆行追踪和免疫组织化学， 在芬氟拉明给药后，我们将确定化学物质 身份和中枢神经系统的网站支配的胡萝卜素激活的神经元，调节 食物摄入量

DESCRIPTION: (Adapted from the Investigator's Abstract) In the United States today aberrant food intake and body weight regulation is prevalent and is manifested by extremes that include obesity and anorexia nervosa. The central nervous system tightly regulates food intake and body weight. Central circuits which utilize serotonin (5HT) exert powerful behavioral effects to decrease body weight. However the mechanism(s) of action of serotonin in regulating feeding and body weight are not understood. Recent studies have established leptin as a fundamental in the regulation of energy balance and neuroendocrine function. Administration of both leptin and serotonergic agonists inhibit food intake. However, it is unknown if leptin and serotonin systems interact within the CNS. Our preliminary findings suggest that leptin engages serotonergic neurons in the dorsal raphe nucleus. We hypothesize that the action of serotonergic systems on feeding converge on leptin-regulated systems as a final common output mechanism and will test these ideas in our specific aims. We will also extend that knowledge to the human brain which will provide fundamental information regarding the mechanisms by which food intake is regulated aberrantly in obesity and in eating disorders such as anorexia nervosa. In this proposal, we outline experiments designed to characterize the neuroanatomic mechanisms by which leptin and serotonin systems interact to regulate food intake. First, we will identify and characterize the chemical identity of hypothalamic neurons that express 5-HT2C and 5-HT1B receptors as these receptors are thought to modulate food intake and body weight. We will use dual label in situ hybridization for 5-HT2C and 5-HT1B mRNA coupled with ISHH for neuropeptides known to regulate food intake. Next, using retrograde tracing and in situ hybridization of 5-HT2C and 5-HT1B receptor mRNA, we will determine if hypothalamic neurons that innervate key autonomic regulatory sites receive serotonergic innervation and express 5-HT1B and 2C receptor mRNA. Third, using retrograde tracing and in situ hybridization for immediate early genes we will determine the CNS sites innervated by leptin-responsive neurons in the dorsal raphe nucleus. Finally, using retrograde tracing and immunohistochemistry for Fos following fenfluramine administration, we will determine the chemical identity and CNS sites innervated by serotonin-activated neurons that regulate food intake.