PEPTIDE REGULATION OF THE CHOROID PLEXUS-CSF SYSTEM

脉络丛-CSF 系统的肽调节

基本信息

批准号：
6529510
负责人：
CONRAD Earl JOHANSON
金额：
$ 30.4万
依托单位：
RHODE ISLAND HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-08-20 至 2005-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6529510
关键词：
arginine vasopressin brain circulation cerebrospinal fluid choroid plexus cytology developmental neurobiology fibroblast growth factor ion transport laboratory rat neuroendocrine system neuroregulation nitric oxide nitric oxide synthase secretion

项目摘要

Choroid plexus (CP) has a great impact on the neuronal extracellular fluid environment. Choroid epithelial cells secrete cerebrospinal fluid (CSF) as well as peptides that modulate brain development, fluid balance and repair following injury and disease. Various growth factors and neuropeptides synthesized in CP are secreted into CSF, thereby exerting endocrine-like effects on target cells in brain as well as local effects on CP. Thus, CP is both a TARGET and a SOURCE for peptides. The renewal projects focus on regulation of the CP-CSF system by peptides, specifically basic fibroblast growth factor (FGF-2) and arginine vasopressin (AVP). The main questions to be answered are: what functions of CP are regulated by FGF-2 and AVP, and how is the release of these peptides from CP to CSF controlled? Both FGF-2 and AVP have been widely implicated in CNS fluid homeostasis, and they are intimately associated with nitric oxide synthase (NOS) which generates nitric oxide (NO). The general working hypothesis is that FGF-2 and AVP, with actions mediated in part by NO, act in concert to reduce choroidal fluid turnover into CSF. Using acute and chronic experimentation in vivo with Sprague- Dawley rats, we will investigate how FGF-2 and AVP alter CP blood flow, CSF-forming capacity and epithelial ultrastructure. Moreover, the rat CP in vitro and the pig CP epithelium monolayer cell cultures will be utilized to analyze mechanisms of peptide effects on cellular organelles, ion transport, and fluid formation. Consequently, the three CP models, investigated with several methodologies, will enable a broad-spectrum analysis of how FGF-2, AVP, NO and other agent interact to regulate CP secretion. Elucidating the ability of FGF-2 and AVP to alter CSF dynamics will provide a larger picture of neuro-endocrine modulation of CNS fluids. Enhanced expression of FGF-2 and AVP in the CP-CSF system following ischemia and hydrocephalus suggests that peptides help to stabilize extracellular fluid volume and composition post-injury. Our long-term goal is to delineate the multifunctional roles of CP in brain fluid homeostasis.

脉络丛（CP）对神经元外流体环境有很大的影响。脉络膜上皮细胞分泌脑脊液（CSF），以及调节脑发育，流体平衡和修复后受伤和疾病后的肽。在CP中合成的各种生长因子和神经肽分泌到CSF中，从而对大脑中的靶细胞产生类似内分泌样的影响以及对CP的局部影响。因此，CP既是肽的靶标，也是肽的来源。更新项目的重点是肽，特别是基本成纤维细胞生长因子（FGF-2）和精氨酸加压素（AVP）对CP-CSF系统的调节。要回答的主要问题是：CP的哪些功能受FGF-2和AVP的调节，以及这些肽从CP到CSF的释放如何控制？ FGF-2和AVP都广泛与CNS液体稳态有关，它们与产生一氧化氮（NO）的一氧化氮合酶（NOS）密切相关。一般的工作假设是，FGF-2和AVP的部分作用是由NO介导的，共同起作用，以减少脉络膜流体的转换为CSF。使用Sprague-Dawley大鼠体内急性和慢性实验，我们将研究FGF-2和AVP如何改变CP血流，CSF形成能力和上皮超微结构。此外，将利用大鼠CP在体外和PIG CP上皮单层细胞培养物来分析肽对细胞细胞器，离子传输和流体形成的作用的机制。因此，使用多种方法研究的三种CP模型将对FGF-2，AVP，NO和其他代理如何相互作用以调节CP分泌的广泛分析。阐明FGF-2和AVP改变CSF动力学的能力将为CNS流体的神经内分泌调制提供更大的了解。缺血和脑积水后，FGF-2和AVP在CP-CSF系统中的表达增强表明，肽有助于稳定细胞外液体体积和损伤后的组成。我们的长期目标是描述CP在脑液体稳态中的多功能作用。