Characterization of Choline Transport by Choroid Plexus

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通路的神经递质。在乙酰胆碱的合成中，胆碱的量是限速的。因此，在大脑神经元的液体中保持适当的胆碱水平对神经元的个体和整体功能都至关重要。这种细胞外液大部分是由脉络膜丛产生的，脉络膜丛是一种非常小的非神经元器官，成年人的平均重量约为2克。它位于脑室或脑腔中。脉络膜丛在调节细胞外液中胆碱以及其他无机和有机离子的水平方面也起着重要作用，通过将胆碱从大脑输送到血液中。更确切地说，脉络膜丛的特化细胞负责将胆碱运输出脑；然而，介导胆碱转运的机制仍然知之甚少。Villalobos博士将定义脉络膜丛运输胆碱的机制，并将研究如何调节这一机制。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，并允许其生长和形成一层相互连接的细胞。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是如何进出脉络丛的。例如，通过这种方式，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细胞的内部支架或细胞骨架，并研究细胞骨架的元素的调节如何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运输的影响。确定胆碱通过脉络膜丛从大脑运输到血液的细胞机制将为进一步探索这一特定运输过程的调节和脑内胆碱水平的调节提供必要的基础信息。

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.