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: 2744691
• 负责人: JOHN D FERNSTROM
• 金额: $ 19.28万
• 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 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2744691
• 关键词: aminoacid metabolism; appetite; behavioral /social science research tag; brain metabolism; dietary proteins; dopamine; ethology; histamine; histidine; hypothalamus; laboratory rat; neurotransmitter biosynthesis; norepinephrine; nutrition related tag; tyrosine

This competing continuation proposal will study in rats the effect of the protein content of single meals and the chronic diet on (a) the central nervous system (CNS) concentration of tyrosine (TYR) and the synthesis rates of the catecholamine neurotransmitters derived from it (dopamine [DA], norepinephrine [NE]); and (b) the animal s self-selection of dietary protein following the administration of TYR or pharmacologic agents that alter DA or NE neurotransmission in brain. Large increases in CNS TYR follow the ingestion of a high-protein meal additionally, CNS TYR drops markedly as chronic protein intake approaches and falls below the rat s maintenance protein requirement; under both diet conditions, parallel changes occur in TYR hydroxylation rate, an index of catecholamine synthesis. This proposal will build on these findings, using a combined behavioral- neurochemical approach. In behavioral studies, we will assess if TYR administration modifies the rat s selection of dietary protein. If so, we will determine the DA and/or NE receptor(s) involved. In biochemical studies, we will determine which catecholamines are affected (DA, NE or both) by changes in protein intake, the brain regions in which they occur (primarily two NE- and DA-containing hypothalamic nuclei involved in food intake control, the paraventricular nucleus and the lateral perifornical hypothalamus), and the relationship of the TYR, DA and NE changes induced by a meal to those caused by alterations in chronic dietary protein intake. A related focus will be to determine if reductions in protein intake below requirement also diminish catecholamine production and release outside the brain (sympathetic nerves, adrenal medulla), and if so, whether sympathetic function declines. A third focus will be brain histidine, which reportedly increases markedly as protein intake falls below requirement levels. We will examine whether such changes occur; if so, whether they enhance the synthesis/turnover in brain histamine, the transmitter synthesized from histidine; and if histamine increases occur, whether they influence appetite for total calories and/or protein (using the self-selection paradigm). Biochemical, pharmacologic, physiological and behavioral approaches will be employed in these studies. Animals (and humans) must meet their nutritional requirement for protein in order to survive and reproduce. An ability to monitor the level of protein intake around the requirement value is thus important. The results of the proposed studies should indicate whether the tyrosine-catecholamine (DA, NE) and/or histidine- histamine relationships provide potential avenues by which the brain can receive information about protein intake, and if so, whether such a signal is employed by the brain to modulate the animal s drive to ingest protein.

这一竞争性延续方案将在大鼠中研究单餐蛋白质含量和慢性饮食对(a)中枢神经系统（CNS）酪氨酸（TYR）浓度及其衍生的儿茶酚胺神经递质（多巴胺[DA]，去甲肾上腺素[NE]）的合成速率的影响；(b)在给予TYR或改变DA或NE神经传递的药物后，动物对膳食蛋白质的自我选择。此外，CNS TYR在摄入高蛋白膳食后大幅增加，随着慢性蛋白质摄入的临近，CNS TYR显著下降，低于大鼠维持蛋白质的需求；在这两种饮食条件下，儿茶酚胺合成指标TYR羟基化率发生平行变化。这项建议将以这些发现为基础，使用行为-神经化学相结合的方法。在行为学研究中，我们将评估TYR是否会改变大鼠对膳食蛋白质的选择。如果是这样，我们将确定所涉及的DA和/或NE受体。在生化研究中，我们将确定哪些儿茶酚胺受到蛋白质摄入变化的影响（DA、NE或两者都有），它们发生的大脑区域（主要是两个含有NE和DA的下丘脑核，参与食物摄入控制，室旁核和外侧下丘脑皮层周围），以及膳食引起的TYR、DA和NE变化与慢性饮食蛋白质摄入改变所引起的变化之间的关系。一个相关的焦点将是确定蛋白质摄入量低于要求是否也会减少儿茶酚胺的产生和释放到大脑外（交感神经，肾上腺髓质），如果是这样，是否交感功能下降。第三个重点将是脑组氨酸，据报道，当蛋白质摄入量低于需求水平时，它会显著增加。我们将研究这种变化是否会发生；如果有，它们是否促进了脑组胺的合成/转换，组胺是由组氨酸合成的递质；如果组胺增加，它们是否会影响对总热量和/或蛋白质的食欲（使用自我选择范例）。这些研究将采用生化、药理学、生理学和行为学方法。为了生存和繁殖，动物（和人类）必须满足它们对蛋白质的营养需求。因此，在需要值附近监测蛋白质摄入水平的能力是很重要的。拟议的研究结果应该表明，酪氨酸-儿茶酚胺（DA， NE）和/或组氨酸-组胺的关系是否提供了大脑接收蛋白质摄入信息的潜在途径，如果是这样，这种信号是否被大脑用来调节动物摄取蛋白质的动力。