Characterization of Choline Transport by Choroid Plexus

IBN98-08616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，胆碱量是限速的。因此，保持大脑中神经元沐浴的液体中适当的胆碱水平，对于神经元的个体和综合功能都是至关重要的。这些细胞外液大部分是由脉络丛产生的，脉络丛是一个非常小的非神经性器官，平均成年人重约2克。它位于大脑的脑室或腔内。脉络丛还通过将胆碱从大脑输送到血液中，在调节细胞外液中胆碱以及其他无机和有机离子的水平方面发挥着重要作用。更准确地说，脉络丛的特殊细胞负责胆碱的脑外运输；然而，调节胆碱运输的机制仍然知之甚少。维拉罗伯斯博士将定义脉络丛运输胆碱的机制，并将研究这一机制可能是如何调节的。在分离的组织中，可以最直接、最有效地研究神经丛中胆碱的运动，并允许生长和改造单个相互连接的细胞。通过使用标记有放射性同位素的胆碱，维拉罗沃斯博士将确定在不同条件下胆碱是如何进入和流出脉络丛的。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，还将使用专门的显微镜观察细胞的内部支架或细胞骨架，并研究细胞骨架元素的调节如何改变脉络丛运输胆碱的能力。用这些方法可以研究物理和化学应激对胆碱转运的影响。通过脉络丛将胆碱从大脑运输到血液的细胞机制的确定，将为进一步探讨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本信息。

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.