Restless Legs Syndrome- The Iron-Dopamine Connection

描述（由申请人提供）：我们为该项目提出了以下核心概念：不宁腿综合征（RLS）症状是由大脑中铁的相对或绝对减少引起的多巴胺能机制改变引起的。这项建议的一个主要目的是整合各学科的活动，使相互关系产生的科学贡献比单独开展每个项目所能产生的贡献更大。本项目的长期目标是确认和更好地说明脑铁不足、DA异常和RLS之间的关系，并确定脑铁不足的原因 以及它与DA系统异常的关系。这将有望导致潜在的新的 RLS的治疗方法，以及可能了解RLS和其他涉及脑铁失调的疾病的新方法。该计划有几个重要的优势：1）许多主要研究者围绕本计划中要解决的具体问题有很长的互动历史：铁和多巴胺及其潜在的相互作用和它们在RLS中的作用。2)强大的，新的调查人员被纳入该计划。3)许多研究人员是脑铁代谢，铁-多巴胺相互作用，人体铁代谢，不宁腿综合征，多巴胺能系统评估的PET技术，铁的MRI定量和使用近交系小鼠的QTL分析等领域的领导者。4)研究人员将使用复杂的PET、MRI、神经病理学、生物学和小鼠近亲繁殖方法， 促进铁，多巴胺的相互作用及其与RLS的相关性的新见解。

DESCRIPTION (provided by applicant): We have proposed the following Core Concept for this project: Restless Legs Syndrome (RLS) symptoms result from altered dopaminergic mechanisms that are precipitated by a relative or absolute reduction of iron in the brain. A major aim of this proposal is to integrate the activities of various disciplines such that the interrelationships will result in a greater scientific contribution than could be achieved if each project were pursued individually. The long-range goal of this Program Project is to confirm and better specify the relationship between brain iron insufficiency, DA abnormalities, and RLS; and also to determine the cause of the brain iron insufficiency in RLS and how it may relate to DA system abnormalities. This would hopefully lead to potential new treatments for RLS and possibly new approaches to understanding RLS and other disorders that involve brain iron dysregulation. The program has several important strengths: 1) Many of the principal investigators have a long history of interaction around the specific issue to be addressed in this Program: Iron and dopamine and their potential interaction and their roles in RLS. 2) Strong, new investigators are integrated into the Program. 3) Many of the investigators are leaders in the fields of brain iron metabolism, iron-dopamine interaction, human iron metabolism, Restless Legs Syndrome, PET techniques for assessment of the dopaminergic system, MRI quantification of iron, and QTL analysis using inbred strains of mice. 4) Investigators will use sophisticated PET, MRI, neuropathological, biological, and mice inbreeding approaches that have been incorporated to facilitate novel insights into the interaction of iron, dopamine and their relevance to RLS.