DIET, AROMATIC AMINO ACIDS, AND CNS NEUROTRANSMITTERS

饮食、芳香氨基酸和中枢神经系统神经递质

• 批准号: 3325578
• 负责人: JOHN D FERNSTROM
• 金额: $ 12.03万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3325578
• 关键词: blood chemistry; brain metabolism; dietary aminoacid; dietary carbohydrates; dietary lipid; dietary proteins; dopamine; electroencephalography; enzyme substrate; fasting; high performance liquid chromatography; insulin; laboratory rat; neurotransmitter biosynthesis; nutrient bioavailability; nutrition related tag; phenylalanine; retina; serotonin; sleep regulatory center; tryptophan; tyrosine; tyrosine 3 monooxygenase

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.

这项研究计划旨在研究饮食如何影响 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 色氨酸（TRP）和酪氨酸（TYR）的摄取， 5 HT和DA的前体，这些变化然后直接改变 5 HT和DA合成。 需要研究的TRP-5 HT问题涉及 描述饮食影响中枢神经系统的机制， TRP摄取和5 HT合成。 特别是一些实验 将定义影响大脑TRP水平的饮食条件 通过血浆大分子中性氨基酸（LNAA）的变化 模式，从而竞争性运输TRP进入大脑。 其他研究将确定大脑TRP水平是否对 饮食脂肪引起的TRP与白蛋白结合的变化， 血液，因为可能有条件下，未结合TRP 促进CNS TRP摄取。 其他实验将 探索饮食引起的变化的行为后果， 5 HT合成。 在这个建议中，睡眠将被研究，因为睡眠- 觉醒行为部分与CNS 5 HT神经元有关。 TYR- DA研究将确定CNS TYR水平和DA合成可以改变， 苯丙氨酸（PHE）作为CNS DA的底物和/或抑制剂 合成以及饮食如何影响CNS PHE水平和DA 合成，以及神经元激活作为一个因素的重要性 决定了DA神经元的哪些CNS亚群将 对酪氨酸和苯丙氨酸诱导的DA变化不敏感 生产 一般的实验设计要求动物 接受一顿饭，注射氨基酸，或 慢性饮食。 此后，血液、大脑和视网膜样本将被 获得，并测定其LNAA（包括 TRP和TYR）和5 HT、DA及其前体， 代谢物。 测量将使用高性能 液相色谱法与荧光或 电化学检测 脑电图睡眠将是 通过皮层和海马的记录进行定量 电极，并在大鼠接受不同的 前体和饮食治疗。 完成后，拟议的 研究应该大大提高我们对 CNS 5 HT和DA合成对前体变化的脆弱性， 以及在何种条件下饮食可以影响 通过改变TRP和TYR（以及 PHE）供应至CNS。