Restless Legs Syndrome- The Iron-Dopamine Connection

描述(申请人提供)：我们为这个项目提出了以下核心概念：不宁腿综合症(RLS)症状是由于大脑中铁的相对或绝对减少而引起的多巴胺能机制的改变。这项建议的一个主要目的是整合不同学科的活动，以便相互联系将产生比单独开展每个项目所能取得的更大的科学贡献。该计划项目的长期目标是确认和更好地确定脑铁缺乏、DA异常和RLS之间的关系；并确定脑铁缺乏的原因 RLS及其与DA系统异常的关系。这有望带来潜在的新的 RLS的治疗，以及可能理解RLS和其他涉及脑铁调节失调的疾病的新方法。该计划有几个重要的优势：1)许多主要研究人员在本计划要解决的具体问题上有很长的互动历史：铁和多巴胺及其潜在的相互作用，以及它们在RLS中的作用。2)强大的新调查人员被整合到该计划中。3)许多研究人员在脑铁代谢、铁-多巴胺相互作用、人类铁代谢、不宁腿综合征、多巴胺能系统的PET技术评估、铁的MRI定量以及利用近交系小鼠进行QTL分析等领域处于领先地位。4)研究人员将使用先进的PET、MRI、神经病理学、生物学和小鼠近亲繁殖方法，这些方法已经被整合到 促进对铁、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.