DOPAMINE - RESTLESS LEGS SYNDROME CONNECTIONS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 不宁腿综合征（RLS）是一种感觉运动障碍，其中多巴胺能系统和脑铁似乎发挥作用。 在超过98%的RLS受试者中对左旋多巴的显著症状反应和用DA拮抗剂诱导的RLS样症状为多巴胺能（DA能）系统在RLS症状产生中的作用提供了令人信服的证据。 尸检、CSF、MRI和IV铁治疗数据表明脑铁缺乏在RLS中的作用。 本提案旨在探索RLS患者DA能系统的差异，评价RLS患者DA能系统昼夜变化的变化，定义RLS患者铁变化与DA能系统变化之间的关系（即脑中还原铁沉淀DA能系统的改变），并确定DA能活性与RLS症状之间是否存在相关性。 本项目的具体目标是： 目的1：通过D2R结合的PET研究来评估RLS患者和对照者之间的多巴胺能差异。 目标二：评价多巴胺能系统的正常昼夜节律变化，并通过比较患者和对照组在7：30 p-11 pm和8：30 am-12：00 pm扫描的PET DA能活性来评估RLS和正常对照组之间这些昼夜节律变化的差异。 目标3：通过DA能系统的PET研究和局部脑铁浓度的MRI测量的相关性，确定RLS中CNS多巴胺系统异常与CNS铁状态之间是否存在任何显著相关性。 目标4：确定DA能活性测量值与RLS症状（通过每日症状日志和每小时周期性腿部运动确定）之间是否存在任何显著相关性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Restless Legs Syndrome (RLS) is a sensory-motor disorder in which the dopaminergic system and brain iron appear to play a role. The dramatic symptomatic response to L-DOPA in over 98% of RLS subjects and the induction of RLS-like symptoms with DA antagonists provide convincing evidence for the role of the dopaminergic (DAergic) system in the production of RLS symptoms. Autopsy, CSF, MRI, and IV iron treatment data indicate a role of brain-iron deficiency in RLS. This Proposal is designed to explore the differences in the DAergic systems in RLS patients, evaluate changes in circadian changes in the DAergic systems in RLS patients, define the relationship between changes in iron and changes in the DAergic system in RLS (i.e. reduced iron in the brain precipitates alterations in DAergic system) and determine if there is correlation between DAeric activity and RLS symptoms. The specific aims of the current Project are: Aim 1: To assess dopaminergic differences between RLS patients and controls by using PET studies of D2R binding. Aim 2: To evaluate the normal circadian changes in the dopaminergic systems and assess differences in these circadian changes between RLS and normal controls by comparing PET DAergic activity in patients and controls scanned 7:30p-11 pm and 8:30am-12:00pm. Aim 3: To determine if there are any significant correlation between the abnormalities in the CNS dopamine system and CNS iron status in RLS by correlation of PET studies of DAergic system and MRI measures of regional brain concentrations of iron. Aim 4: To determine if there is any significant correlation between measurements of DAergic activity and RLS symptoms (determined by daily symptom log and periodic leg movements per hour).