DIETARY AMINO ACID DISPROPORTION--NEURAL RESPONSES

膳食氨基酸歧化——神经反应

• 批准号: 3464089
• 负责人: DOROTHY W GIETZEN
• 金额: $ 9.22万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3464089
• 关键词: anorexia; brain metabolism; dietary aminoacid; experimental brain lesion; neuroanatomy; neurochemistry; neuropharmacology; nutrition disorder chemotherapy; nutrition related tag; serotonin inhibitor; serotonin receptor

DESCRIPTION (Adapted from Investigator's Abstract): Disorders of food intake are associated with increased morbidity and mortality. The nutritional problem of amino acid (AA) disproportionality is associated with anorectic responses. A better understanding of the mechanisms underlying these responses may yield insight into certain anorexias and provide information about the role of AA's in the control of food intake. Replacement of the limiting (Lim) AA into a precise brain area known to be essential for the anorectic response will ameliorate the feeding depression suggesting that the decrease in the limiting AA is sensed there. The serotonin (5HT) system is also activated in animals eating imbalanced AA diets, and importantly, blockade of the 5HT3 receptor can dramatically increase intake of these diets. However, in spite of considerable evidence favoring the brain as the site of control in AA imbalance, recent preliminary studies suggest that the 5HT3 antagonist may be acting at a peripheral site in remediating the anorexia associated with an AA imbalance. The studies of the present proposal are designed to explore the role of the 5HT system further, in an attempt to understand how and where it functions to mediate the anorectic response to AA imbalance. Specific Aim 1 addresses the specificity of the 5HT system in this nutritional model. Specific Aim 2 is to determine the locus of the activity of the 5HT3 system in this model. Specific Aim 3 is to test the hypotheses that (a) the development of a conditioned taste aversion (CTA) may be the final common pathway in the feeding depression with AA imbalance, and (b) the 5HT3 receptor is involved in this aspect of the response. Finally, an investigation of the mechanisms underlying the depressed feeding responses to AA excess will be initiated as Specific Aim #4, using a neurochemical survey similar to that used earlier with deficiency in the AA imbalance model. These studies will utilize purified L-AA's as the protein equivalent in defined diets, with food intake as the experimental outcome. The applicant will use neurochemical measurements, neuroanatomical lesions and neuropharmacological interventions as tools for determining the mechanisms underlying the depression in feeding with AA excess and deficiency.

描述（改编自研究者摘要）：食物失调 摄入量与发病率和死亡率增加有关。 这 氨基酸（AA）不成比例的营养问题与此相关 伴有厌食反应。 更好地理解机制 这些反应的背后可能会深入了解某些厌食症和 提供有关 AA 在控制食物摄入中的作用的信息。 将限制性 (Lim) AA 替换为已知的精确大脑区域 对于厌食反应至关重要，将改善进食抑制 表明在那里感觉到了限制 AA 的减少。 这 食用不平衡 AA 的动物也会激活血清素 (5HT) 系统 饮食，重要的是，阻断 5HT3 受体可以显着 增加这些饮食的摄入量。 然而，尽管有大量证据 最近，有利于大脑作为 AA 失衡的控制部位 初步研究表明 5HT3 拮抗剂的作用可能是 外周部位治疗与 AA 相关的厌食症 不平衡。 本提案的研究旨在探索 进一步了解 5HT 系统的作用，试图了解如何以及在何处 它的作用是调节对 AA 不平衡的厌食反应。 具体的 目标 1 解决了 5HT 系统在该营养领域的特殊性。 模型。 具体目标 2 是确定 该型号采用5HT3系统。 具体目标 3 是检验以下假设： (a) 条件性味觉厌恶（CTA）的发展可能是最终的结果 AA 失衡导致进食抑制的共同途径，以及 (b) 5HT3 受体参与这方面的反应。 最后，一个 研究抑制进食反应的机制 AA 过量将作为具体目标 #4 启动，使用神经化学物质 类似于之前使用的调查，但 AA 不平衡不足 模型。 这些研究将利用纯化的 L-AA 作为蛋白质 等同于规定的饮食，以食物摄入量作为实验结果。 申请人将使用神经化学测量、神经解剖学病变 和神经药理学干预作为确定的工具 AA过量喂养导致抑郁的机制 不足。