Characterization of Choline Transport by Choroid Plexus

脉络丛胆碱转运的表征

• 批准号: 9808616
• 负责人: J. Larry Renfro
• 金额: $ 11.19万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 2001-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9808616&HistoricalAwards=false
• 关键词: Characterization; Choline; Transport; Choroid; Plexus

IBN98-08616 VILLALOBOS Choline is an immediate precursor to acetylcholine, the neurotransmitter for the central neuronal pathways involved in sleep-wake cycling and learning or memorization. The amount of choline is rate-limiting in the synthesis of acetylcholine. Therefore, maintaining appropriate levels of choline in the fluid that bathes the neurons in the brain is critical to both their individual and integrative function. Most of this extracellular fluid is produced by the choroid plexus, a very small non-neuronal organ, weighing about 2 grams in the average adult human. It is located in the ventricles, or cavities, of the brain. The choroid plexus also plays an important role in regulating the levels of choline, as well as other inorganic and organic ions, in the extracellular fluid by transporting choline from the brain into the blood. More precisely, specialized cells of the choroid plexus are responsible for the transport of choline out of brain; however, the mechanism that mediates choline transport remains poorly understood. Dr. Villalobos will define the mechanism by which choroid plexus transports choline and will investigate how this mechanism might be modulated. The movement of choline by plexus can be most directly and effectively studied in tissues that are isolated and allowed to grow and reform a single sheet of interconnected cells. Using choline labeled with radioactive isotopes, Dr. Villalobos will determine how choline is transported into and out of the choroid plexus under different conditions. In this manner, for example, the dependence of choline transport on sodium and potassium can be determined. In addition, a specialized microscope will be used to visualize the internal scaffolding, or cytoskeleton, of the cell and to study how modulation of elements of the cytoskeleton may alter the ability of choroid plexus to transport choline. With these methods the effects of physical and chemical stress on choline transport will a lso be investigated. Determination of the cellular mechanism by which choline is transported from the brain to the blood by choroid plexus will provide the basic information necessary to probe further both the regulation of this specific transport process and the regulation of choline levels in the brain.

IBN 98 -08616 VILLALOBOS 胆碱是乙酰胆碱的直接前体，乙酰胆碱是参与睡眠-觉醒循环和学习或记忆的中枢神经元通路的神经递质。 胆碱的量在乙酰胆碱的合成中是限速的。 因此，在大脑中浸泡神经元的液体中保持适当水平的胆碱对它们的个体和综合功能都至关重要。 大多数细胞外液是由脉络丛产生的，脉络丛是一个非常小的非神经器官，平均成年人重约2克。 它位于脑室或脑腔中。 脉络丛还通过将胆碱从脑转运到血液中，在调节细胞外液中胆碱以及其他无机和有机离子的水平中起重要作用。 更确切地说，脉络丛的专门细胞负责将胆碱运输出大脑;然而，介导胆碱运输的机制仍然知之甚少。 Villalobos博士将定义脉络丛运输胆碱的机制，并将研究如何调节这种机制。 胆碱通过神经丛的运动可以在分离的组织中进行最直接和有效的研究，这些组织可以生长并改革成单层相互连接的细胞。 使用放射性同位素标记的胆碱，Villalobos博士将确定胆碱在不同条件下如何进出脉络丛。 以这种方式，例如，可以确定胆碱转运对钠和钾的依赖性。 此外，一个专门的显微镜将用于可视化的内部支架，或细胞骨架，细胞和研究细胞骨架的元素的调制如何可能改变脉络丛运输胆碱的能力。利用这些方法还将研究物理和化学胁迫对胆碱转运的影响。 确定胆碱通过脉络丛从脑转运到血液的细胞机制，将提供进一步探索这种特定转运过程的调节和脑中胆碱水平的调节所需的基本信息。