INTEGRATIVE RESPONSES TO AMINO ACID DEFICIENCY

充足的氨基酸(AA)营养对健康和 人类和动物的幸福。由于AA没有存储池，因此 一种不可缺少的氨基酸(IAA)缺乏症可能会迅速发生， 尤其是如果已经存在轻度蛋白质缺乏的情况下。AA 已经证明，缺陷会损害生长和任何身体功能， 取决于蛋白质的合成，比如伤口的愈合。此外，IAA失衡 会导致一种众所周知的厌食反应。由于AA补充剂已经成为 时尚，特别是在“健康食品”爱好者、节食者和运动员中， IAA失衡应被视为一种潜在的健康危害。此外，许多人 IAA比例失调使人类疾病复杂化。鉴于AA的重要性 在营养方面，必须更好地了解基本情况 对IAA缺乏症的反应是通过 大脑。该实验室工作的长期目标是了解如何 IAA缺乏是由身体识别的，以及这种缺乏如何导致 进食量减少。IAA不平衡饮食(1MB)是一种极好的 这些研究的营养模型，如生化和行为 反应强劲、迅速，而且描述得很好。梨状皮质前叶 大脑的(APC)似乎是IAA缺乏的化学传感器；然而， APC不能单独采取行动来引起厌食反应。因此，这些信号 由APC产生的必须与其他大脑区域整合，可能在 前脑，改变进食行为。这项提议的目标是 来确定大脑整合大脑的电路和机制 初始响应为1MB。我们建议通过以下途径实现这些目标 具体目标1，识别前脑内的神经回路 整合来自APC的感觉信号并激活其他大脑 启动对TMB的厌食反应的区域；具体目标2，以确定 介导对1MB反应的神经化学机制和特定的目的 3，以确定该神经回路的激活顺序和 信令机制。

Adequate amino acid (AA) nutrition is essential for the health and well being of humans and animals alike. Because AAs have no storage pool, the development of an indispensable amino acid (IAA) deficiency can occur rapidly, particularly if a mild state of protein deficiency already exists. AA deficiencies have been shown to compromise growth and any bodily function that depends on protein synthesis, such as wound healing. In addition, IAA imbalance leads to a well-described anorectic response. Since AA supplements have become fashionable, especially among "health food" faddists, dieters, and athletes, IAA imbalance should be recognized as a potential health hazard. Moreover, many human diseases are complicated by IAA disproportion. Given the importance of AA nutrition, it is imperative to gain a better understanding of the basic mechanisms by which the responses to IAA deficiency are integrated by the brain. The long term goals of the work in this laboratory are to understand how IAA deficiency is recognized by the body and how this deficiency causes the depression of food intake. The IAA imbalanced diet (1MB) is an excellent nutritional model for these studies, as the biochemical and behavioral responses are robust, rapid and well described. The anterior piriform cortex (APC) of the brain appears to be the chemosensor for IAA deficiency; however, the APC cannot act alone to cause the anorectic response. Thus, the signals generated by the APC must be integrated with other brain areas, likely in the anterior forebrain, to change eating behavior. The goals of this proposal are to determine the circuitry and mechanisms by which the brain integrates the initial response to 1MB. We propose to achieve these goals through the following: Specific Aim 1, to identify the neural circuit within the forebrain that integrates the sensory signals from the APC and activates other brain areas to initiate the anorectic responses to TMB; Specific Aim 2, to determine the neurochemical mechanisms that mediate the response to 1MB; and Specific Aim 3, to determine the order of activation in this neural circuit and the signaling mechanisms.