REGIONAL BLOOD-BRAIN BARRIER TRANSPORT OF AMINO ACIDS

大脑严重依赖于循环的血液来提供 必需营养素：用于能量代谢的葡萄糖和酮体， 氨基酸是蛋白质和神经递质，胆碱是乙酰胆碱， 核苷、嘌呤和嘧啶用于核苷酸、RNA和DNA。 每种化合物进入的限速步骤似乎是 通过血脑屏障，这是由饱和的 传输过程服从Michaelis-Menten动力学。 血脑 屏障运输系统在管制进入方面处于独特的地位， 必需的营养素，从而影响大脑功能。 已经 至少有一种病理状态，肝性脑病， 不同种类的营养物质的运输在一个 特色的方式。 有充分的理由相信， 其他病理状态如糖尿病、甲状腺功能减退和尿毒症， 也将被改变。 直到最近，所有关于血脑的研究 屏障转运已在全脑中进行。 的进一步发展 我们对大脑功能的了解需要了解这些 结构层面的过程，以及实现这一目标的方法， 确立了习 本建议的目的是研究当地的 在个体脑水平上运输各种必需底物 使用原理中开发的放射自显影技术的结构 调查员的实验室。 主要工作将是研究 几种病理状态下转运系统的分布 包括甲状腺功能减退尿毒症和糖尿病 这些数据将允许 确定血脑变化的位置和幅度 屏障，并使其与疾病的相关性的评估成为可能 过程

The brain is critically dependent on the circulating blood for a supply of essential nutrients: glucose and ketone bodies for energy metabolism, amino acids for protein and neurotransmitters, choline for acetylcholine, and nucleosides, purines and pyrimidines for nucleotides, RNA, and DNA. The rate-limiting step for entry of each of these compounds appears to be passage across the blood-brain barrier, which is mediated by saturable transport processes obeying Michaelis-Menten kinetics. The blood-brain barrier transport systems are in a unique position to regulate the entry of essential nutrients and thereby affect brain function. It has been established at least in one pathological condition, hepatic encephalopathy, that the transport of different classes of nutrients are altered in a characteristic way. There is good reason to believe that transport in other pathological states such as diabetes, hypothyroidism, and uremia, will also be changed. Until recently, all studies examining blood-brain barrier transport have been conducted in whole brain. Further advances in our knowledge of brain function require the understanding of these processes at the structural level, and methods for achieving this have been established. It is the purpose of this proposal to study the local transport of various essential substrates at the level of individual brain structures using an autoradiographic technique developed in the principal investigator's laboratory. The primary effort will be to study the distribution of transport systems in several pathological situations including hypothyroidism, uremia, and diabetes. The data will allow the determination of the location and magnitude of changes in the blood-brain barrier and make possible the evaluation of their relevance to the disease process.