THE IRON-DOPAMINE CONNECTION

该项目的具体目标是确定脑铁浓度变化的程度，这种变化是自然表型变化，还是由饮食铁限制引起的增强表型，导致DA合成、释放、再摄取和动力学的改变，以及它们对运动反射活动和运动活动昼夜节律调节的相关影响。本项目的长期计划是建立RLS动物模型，但目前的重点是建立生物学模型，探索铁与多巴胺能系统的关系。在本项目中，我们利用两株重组近交系小鼠来探索脑铁变异改变DA系统及其相关行为的潜在机制。

The specific goal of this project is to determine the extent to which variations in brain iron concentration, that occur as a natural phenotypic variation, or as augmented phenotypes induced by dietary iron restriction, result in alterations of DA synthesis, release, re-uptake, and kinetics, and their associated impact upon motor reflex activity and circadian regulation of motor activity. The long-term plan of this project is to establish an animal model for RLS, but the immediate focus is to establish a biological model for exploring the relationship of iron to the dopaminergic system. In this project, we utilize two strains of recombinant inbred strains of mice to explore the potential mechanisms through which brain iron variances can alter the DA system, and associated behaviors. The aims of the current project are: Aim 1: To determine the extent to which brain iron variances can effect DA metabolism during the active and inactive phases of the diurnal cycle. Aim 2: To assess the degree to which brain iron variance results in alterations in behaviors regulated by DA pathways. Aim 3: To determine the extent to which brain iron variance will alter the "normal" DA response to chronic DA agonist treatment. Aim 4: To explore how chronic treatment with L-dopa will affect the behaviors explored in Aim 2.