Developing a behavioral model of Restless Legs Syndrome utilizing mice with natural variances in ventral midbrain iron

• Published in: Sleep medicine 2020-07, Vol.71, p.135-140
• Main Authors: Earley, Christopher J., Allen, Richard P., Jones, Byron C., Unger, Erica L.
• Format: Article
• Language: English
• Subjects: Activity; Iron; Mice; Recombinant inbred; Restless leg syndrome; Ventral midbrain
• ISSN: 1389-9457; 1878-5506
• DOI: 10.1016/j.sleep.2019.12.007

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. 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. 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