INTEGRATIVE RESPONSES TO AMINO ACID DEFICIENCY

充足的氨基酸（AA）营养对健康和健康至关重要- 人类和动物都一样。 由于AA没有存储池， 一个基本的AA缺乏症的发展可能会迅速发生，特别是 如果已经存在轻微的蛋白质缺乏症。 自AA以来 补充剂已经变得时尚，并且特别可能被使用， 对于节食者来说，AA失衡应该被认为是一种潜在的健康危害。 此外，患有癌症恶病质、AA代谢紊乱、 其他代谢异常也可能患有AA比例失调。 AA 已经证明缺乏会损害生长和任何身体功能 这取决于蛋白质的合成，比如伤口的愈合。 但 由于AA不平衡导致的增长减少实际上是次要的， 食物摄入减少，对AA缺乏的厌食反应。 的 这个实验室工作的长期目标是了解AA是如何 缺乏是由身体认识，以及如何表达这种缺乏 在一个现成的行为测量中，食物摄入量。 鉴于 重要的AA营养，当务之急是我们获得一个更好的 了解AA失衡影响的基本机制 摄食行为 使用AA不平衡（IMB）饮食的明确定义的营养模型是 可用于这些研究。 前梨状前皮质（PPC） 大脑被认为是AA传感器的主要候选者 IMB饮食模型的缺陷。 然而，两个封锁的 外周和迷走神经切断术中的5-羟色胺/3受体也调节 IMB饮食。 因此，在几个系统之间必须发生相互作用 已经知道在IMB饮食的反应中发挥作用，以及与 其他系统，可能会揭示在这里提出的研究。 PPC 阻断对IMB饮食的厌食反应的病变通常较大 足以冲击到相邻的结构或纤维的通道， 大脑区域，但不知道哪些神经通路参与其中 在PPC和其他相关系统之间建立关联，例如 迷走神经系统 因此，我们假设对一个或多个 另外的大脑区域在反应中可能是重要的。 具体目标1 除了PPC之外，我们还将识别出 在最初的厌食反应时激活，使用分子 立即早期基因（IEG）的探针，作为神经系统疾病的标记物， 活动和特定病变。 其次，几种特定的神经化学物质 在以前的研究中已经发现了变化， 神经递质和其他AA代谢物在神经化学反应 IMB饮食，主要是在PPC。 具体目标2将确定是否 神经化学变化，类似于那些已经观察到的PPC，发生 在IEG研究中定义的其他领域，并定义受体 涉案 具体目标3将解决这些问题之间的相互作用 几个系统，使用神经化学，神经外科和 神经药理学技术

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 essential AA deficiency can occur rapidly, particularly if a mild state of protein deficiency already exists. Since AA supplements have become fashionable, and may especially be used by dieters, AA imbalance should be recognized as a potential health hazard. Moreover, individuals with cancer cachexia, disorders of AA metabolism, and other metabolic aberrancies may also suffer AA disproportion. AA deficiencies have been shown to compromise growth and any bodily function that depends on protein synthesis, such wound healing. However, the growth reduction attributed to AA imbalance is actually secondary to the decreased food intake, an anorectic response to the AA deficiency. The long-term goal of the work in this laboratory is to understand how AA deficiency is recognized by the body, and how this deficiency is expressed in a readily available behavioral measure, food intake. Given the importance of AA nutrition, it is imperative that we gain a better understanding of the basic mechanisms by which AA imbalance affects feeding behavior. A well defined nutritional model using AA imbalanced (IMB) diets is available for these studies. The anterior prepyriform cortex (PPC) of the brain has been implicated as the prime candidate for the sensor of AA deficiency in the IMB-diet model. However, both blockade of the serotonin/3 receptor in the periphery nd vagotomy also modulate intake of IMB diets. Thus, interactions must occur among the several systems already known to play roles in the responses to IMB diets, as well as with other systems that may be revealed in the studies proposed here. PPC lesions that block the anorectic response to IMB diets usually are large enough to impinge on adjacent structures or fibers of passage to other brain regions, but it is not known what neural pathways are involved in making associations between the PPC and other implicated systems, such as the vagal system. Thus, we hypothesize that projections to one or more additional brain areas may be important in the response. Specific Aim 1 will be to identify the brain areas, in addition to the PPC, that are activated at the time of the initial anorectic response, using molecular probes for immediate early gene (IEG) that serve as markers for neural activity and specific lesions. Second, several specific neurochemical alterations have been found in previous studies, implicating neurotransmitters and other AA metabolites in the neurochemical responses to IMB diets, chiefly in the PPC. Specific Aim 2 will be to determine if neurochemical changes, similar to those already observed in the PPC, occur in the other areas defined in the IEG studies, and to define the receptors involved. Specific Aim 3 will address the interactions among these several systems, using neurochemical, neurosurgical and neuropharmacological techniques.