Choroid plexus control of cerebrospinal fluid inorganic phosphate

脉络丛对脑脊液无机磷酸盐的控制

• 批准号: 0843253
• 负责人: J. Larry Renfro
• 金额: $ 44.38万
• 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: 2009
• 资助国家: 美国
• 起止时间: 2009-02-15 至 2015-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0843253&HistoricalAwards=false
• 关键词: Choroid; plexus; control; cerebrospinal; fluid

The choroid plexus is a tissue located in spaces (ventricles) in the brain and forms about 70% of the cerebrospinal fluid (CSF). The CSF both mechanically cushions and, in large part, determines the stability of the chemical environment of the neurons. The CSF is similar to plasma but has very little protein, higher chloride, and substantially less inorganic phosphate. The mechanisms responsible for maintaining the CSF phosphate concentration at a lower level is unknown, but it is hypothesized that control of CSF phosphate is due, in part, to active removal of phosphate by the choroid plexus. The overall objective of this project is to determine the mechanism and control of active phosphate transport by the choroid plexus. Two model systems for these studies are the sheet-like choroid plexus of a shark and a mammalian immortalized choroid plexus cell line that can be maintained in a functional state outside the body. Unlike mammalian choroid plexus in its natural state inside the brain, which is highly enfolded, frond-like and deep within brain tissue, the choroid plexus of the shark normally forms a large slightly enfolded sheet on the surface of the brain. The latter allows the use of special chambers for the determination of the mechanisms of transfer of phosphate out of the CSF back into the blood. The molecular mechanisms responsible for the phosphate transfer process will be identified by knocking down the expression of specific transport proteins and monitoring the effect on phosphate transport. Once identified in the shark, similar transport systems will be sought in the mammalian system reorganized in culture into a sheet-like tissue. Another objective of the project is to determine how this phosphate transfer system is controlled by focusing on parathyroid hormone-related peptides. These peptides are involved in regulating calcium and phosphate metabolism and it is hypothesized that they regulate CSF phosphate concentration through actions on the choroid plexus phosphate transport processes. Because small changes in CSF can have very large effects on brain function as well as alter other processes such as breathing rate, factors which modulate its composition will have important effects on normal body functions. This project will involve the training of undergraduate and graduate students and participation in NSF Research Experience for Undergraduate programs at the University of Connecticut and Mount Desert Island Biological Laboratory.

脉络膜丛是位于脑室的组织，约占脑脊液（CSF）的70%。脑脊液不仅在机械上起到缓冲作用，而且在很大程度上决定了神经元化学环境的稳定性。脑脊液与血浆相似，但蛋白质含量很少，氯含量较高，无机磷酸盐含量较低。维持CSF磷酸盐浓度在较低水平的机制尚不清楚，但假设CSF磷酸盐的控制部分是由于脉络膜丛主动去除磷酸盐。该项目的总体目标是确定通过脉络丛的活性磷酸盐运输的机制和控制。这些研究的两个模型系统是鲨鱼的片状脉络膜丛和哺乳动物的永生化脉络膜丛细胞系，这些细胞系可以在体外维持在功能状态。哺乳动物的脉络膜丛在大脑内部的自然状态下是高度包裹的，像叶子一样，位于脑组织深处，而鲨鱼的脉络膜丛通常在大脑表面形成一个稍微包裹的大薄片。后者允许使用特殊的腔室来确定磷酸盐从CSF转移回血液的机制。磷酸盐转运过程的分子机制将通过敲除特定转运蛋白的表达和监测对磷酸盐转运的影响来确定。一旦在鲨鱼身上发现了类似的运输系统，将在哺乳动物系统中寻找在培养中重组成片状组织的系统。该项目的另一个目标是通过关注甲状旁腺激素相关肽来确定这种磷酸盐转移系统是如何控制的。这些肽参与调节钙和磷酸盐代谢，并推测它们通过对脉络膜丛磷酸盐运输过程的作用来调节CSF磷酸盐浓度。由于脑脊液的微小变化会对大脑功能产生很大的影响，也会改变呼吸频率等其他过程，因此调节脑脊液成分的因素将对正常的身体功能产生重要影响。该项目将包括本科生和研究生的培训，并参与康涅狄格大学和Mount Desert Island生物实验室的NSF本科生研究经验项目。