DIET, AROMATIC AMINO ACIDS, AND CNS NEUROTRANSMITTERS

这项研究计划旨在研究饮食如何影响人的健康 两种中枢神经系统(CNS)神经递质的合成 5-羟色胺(5-HT)和多巴胺(DA)。生化/代谢 实验的基础是食物摄入改变了中枢神经系统 摄取氨基酸色氨酸(Trp)和酪氨酸(TYR) 5-羟色胺和多巴胺的前体，这些变化直接改变 5-羟色胺和多巴胺合成。色氨酸-5羟色胺有待研究的问题 描述饮食影响中枢神经系统的机制 色氨酸摄取和5-羟色胺合成。特别是，一些实验 将定义影响大脑色氨酸水平的饮食条件 通过血浆大中性氨基酸(LNAA)的变化 模式，从而将色氨酸竞争性运输到大脑中。 其他研究将确定大脑色氨酸水平是否对 膳食脂肪对大鼠血清色氨酸蛋白结合力的影响 血液，因为在某些情况下可能会解开色氨酸 白蛋白可促进中枢神经系统色氨酸的摄取。其他实验将会 探讨饮食引起的饮食变化的行为后果 5-羟色胺合成。在这项提案中，将研究睡眠，因为睡眠- 觉醒行为部分与中枢神经系统5-羟色胺神经元有关。TYR- DA研究将定义中枢神经系统在何种饮食条件下 酪氨酸水平和DA合成可以改变，重要的是 苯丙氨酸(Phe)作为中枢神经系统DA的底物和/或抑制剂 合成及其饮食对中枢神经系统苯丙氨酸和多巴胺的影响 合成，以及神经元激活作为一个因素的重要性 决定哪些中枢神经系统DA神经元亚群将会和将会 对TYR和Phe诱导的DA变化不敏感 制作。总体实验设计要求动物 接受一顿饭，一种氨基酸的注射，或者一次 长期节食。此后，血液、大脑和视网膜样本将 获得LNAA，并对其含量进行检测(包括 色氨酸和酪氨酸)和5-羟色胺、多巴胺及其前体和 代谢物。测量将使用高性能 高效毛细管气相色谱-荧光法 电化学检测。脑电睡眠将会是 通过大脑皮层和海马区的记录进行定量 电极，并研究后大鼠收到不同的 前体和饮食治疗。完成后，建议的 学习应该会大大提高我们对 中枢5-羟色胺和多巴胺合成对前体变化的易感性， 以及饮食在哪些情况下会影响 通过改变Trp和TYR(和 Phe)向CNS供应。

The research plan porposes to study how diet influences the syntheses of two central nervous system (CNS) neurotransmitters, serotonin (5HT) and dopamine (DA). The biochemical/metabolic basis for the experiments is that food ingestion modifies the CNS uptake of tryptophan (TRP) and tyrosine (TYR), the amino acid precursors of 5HT and DA, and these changes then directly alter 5HT and DA synthesis. The TRP-5HT issues to be studied deal with characterizing the mechanisms by which diet influences CNS TRP uptake and 5HT synthesis. In particular, some experiments will define the dietary conditions that influence brain TRP level via changes in the plasma large neutral amino acid (LNAA) pattern, and thus the competitive transport of TRP into brain. Other studies will determine if brain TRP levels respond to dietary fat-induced changes in the albumin binding of TRP in blood, since there may be conditions under which unbinding TRP from albumin promotes CNS TRP uptake. Other experiments will explore for behavioral consequences of diet-induced changes in 5HT synthesis. In this proposal, sleep will be studied since sleep- waking behavior is linked in part to CNS 5HT neurons. The TYR- DA studies will define the dietary conditions under which CNS TYR levels and DA synthesis can be changed, the importance of phenylalanine (PHE) as a substrate and/or inhibitor of CNS DA synthesis and how diet influences CNS PHE levels and DA synthesis, and the importance of neuronal activation as a factor dictating which CNS subpopulations of DA neurons will and will not be sensitive to TYR-and PHE-induced changes in DA production. The general experimental design calls for animals to receive either a single meal, an injection of an amino acid, or a chronic diet. Thereafter, blood, brain and retinal samples will be obtained, and assayed for their contents of the LNAA (including TRP and TYR) and of 5HT, DA, and their precursors and metabolites. Measurements will be made using high-performance liquid chromatography coupled with fluorescence or electrochemical detection. Electroencephalographic sleep will be quantitated via recordings from cortical and hippocampal electrodes, and studied after rats have received different precursor and dietary treatments. When completed, the proposed studies should greatly enhance our understanding of the vulnerability of CNS 5HT and DA synthesis to precursor changes, and of the conditions under which the diet can influence the formation of these transmitters by altering TRP and TYR (and PHE) supply to the CNS.