BACKGROUND The primary symptoms of Restless Legs Syndrome (RLS) are circadian-dependent, leading to increased activity or decreased rest, especially at night. The primary pathology in RLS is brain iron insufficiency despite normal systemic iron stores. Natural variances in brain and peripheral iron concentrations across recombinant inbred (RI) murine strains provide a biological model of RLS. The question is whether these RI mice strains show a behavioral analog to circadian-dependent clinical phenotype of RLS. METHODS The home cage activity of eight female RI strains was measured over a 72-h period. The ratio of the average activity in the last 2 h of the active period relative to that in the total 12-h active period (late active period activity ratio, LAPAR) was the primary outcome variable. The relation of average LAPAR scores to measures of ventral midbrain (VMB) iron was evaluated across strains in this study. RESULTS RI strain 40 (LAPAR = 1.28) and RI strain 21 (LAPAR = 1.02) were the only strains to show an increased activity in the last part of the active period. ANOVA showed the increased activity was significantly greater during the last 2 h compared to the preceding 10 h of the active phase only for the RI strain 40. Average LAPAR across the eight strains did not significantly correlate with the VMB iron content (r = -0.27, p < 0.10) but did correlate with changes in VMB iron with iron deficiency (r = 0.71, p < 0.05) and diurnal change in VMB iron (r = 0.65, p < 0.05). CONCLUSION The female RI strain 40 mice exhibited a distinct end-of-active-period behavior analogous to circadian-dependent clinical phenotype of RLS.

中文翻译：

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利用腹侧中脑铁自然变异的小鼠开发不安腿综合症的行为模型。

背景不宁腿综合症（RLS）的主要症状与昼夜节律相关，导致活动增加或休息减少，尤其是在夜间。尽管全身铁储存正常，但不宁腿综合征的主要病理是脑铁不足。重组近交 (RI) 小鼠品系的大脑和外周铁浓度的自然差异提供了 RLS 的生物学模型。问题是这些 RI 小鼠品系是否表现出与昼夜节律依赖性 RLS 临床表型相似的行为。方法 对 8 只雌性 RI 品系在 72 小时内的笼内活动进行了测量。活动期最后 2 小时的平均活动量相对于总 12 小时活动期的平均活动量的比率（后期活动期活动率，LAPAR）是主要结果变量。本研究评估了不同品系的平均 LAPAR 评分与腹侧中脑 (VMB) 铁测量的关系。结果 RI 菌株 40 (LAPAR = 1.28) 和 RI 菌株 21 (LAPAR = 1.02) 是唯一在活跃期最后部分表现出活性增加的菌株。方差分析显示，与仅 RI 菌株 40 的活性阶段的前 10 小时相比，最后 2 小时的活性增加显着更大。八个菌株的平均 LAPAR 与 VMB 铁含量没有显着相关性 (r = -0.27 ，p < 0.10），但确实与缺铁时 VMB 铁的变化（r = 0.71，p < 0.05）和 VMB 铁的昼夜变化（r = 0.65，p < 0.05）相关。结论 雌性 RI 品系 40 小鼠表现出明显的活跃期末期行为，类似于 RLS 的昼夜节律依赖性临床表型。