REGIONAL BLOOD-BRAIN BARRIER TRANSPORT OF AMINO ACIDS

大脑严重依赖于循环中的血液供应 必需营养素：能量代谢的葡萄糖和酮体， 蛋白质和神经递质的氨基酸，乙酰胆碱的胆碱， 核苷酸、RNA和DNA的核苷、嘌呤和嘧啶。 进入这些化合物的限速步骤似乎是 通过血脑屏障，这是由饱和物质介导的 转运过程服从Michaelis-Menten动力学。血脑 屏障运输系统处于独特的地位，可以监管进入 必需的营养物质，从而影响大脑功能。一直以来 至少在一种病理条件下确诊，肝性脑病， 不同种类营养物质的运输在一种 独具特色的方式。我们有充分的理由相信， 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，所有检测血脑的研究 屏障转运已经在整个大脑中进行。在以下方面取得进一步进展 我们对大脑功能的了解需要了解这些 结构层面的流程和实现这一目标的方法 已经成立了。这项建议的目的是研究当地的 多种必需底物在个体脑水平的转运 使用放射自显影技术的结构，该技术在 调查员的实验室。主要的努力将是研究 运输系统在几种病理情况下的分布 包括甲状腺功能减退症、尿毒症和糖尿病。该数据将允许 确定血脑变化的位置和大小 障碍，并使评估其与疾病的相关性成为可能 进程。

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.