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， 不可或缺的氨基酸（IAA）缺乏症可能会迅速发生， 特别是如果已经存在轻微的蛋白质缺乏状态。AA 已经证明缺乏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 会导致厌食反应由于AA补充剂已成为 时尚，特别是在“健康食品”时尚，节食，和运动员， IAA失衡是一种潜在的健康危害。而且很多 人类的疾病因IAA比例失调而变得复杂。鉴于AA的重要性 因此，有必要更好地了解基本营养， IAA缺乏的反应被整合的机制， 个脑袋本实验室工作的长期目标是了解 IAA缺乏症是由身体识别，以及这种缺乏症如何导致 食物摄入量减少。IAA不平衡饮食（1 MB）是一个很好的 这些研究的营养模型，作为生物化学和行为 反应是有力的、迅速的和有充分描述的。梨状皮质前部 (APC)大脑的皮层似乎是IAA缺乏的化学传感器;然而， APC不能单独作用以引起厌食反应。因此，信号 由APC产生的信号必须与其他大脑区域整合，可能在 前脑前部，改变饮食行为。本提案的目标是 以确定大脑整合大脑的电路和机制， 初始响应为1 MB。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，确定 介导对1 MB的反应的神经化学机制;和特定目标 3、确定该神经回路中的激活顺序， 信号机制。

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.