Developing a Behavioral Model of Restless Legs Syndrome Utilizing Mice with Natural Variances in Ventral Midbrain Iron

Overview

Journal Sleep Med

Specialties Neurology
Psychiatry

Date 2020 Feb 12

PMID 32044226

Citations 4

Authors

Christopher J Earley

Richard P Allen

Byron C Jones

Erica L Unger

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Effects of iron-deficient diet on sleep onset and spinal reflexes in a rodent model of Restless Legs Syndrome.

Woods S, Basco J, Clemens S Front Neurol. 2023; 14:1160028.

PMID: 37273717 PMC: 10234126. DOI: 10.3389/fneur.2023.1160028.

Putative Animal Models of Restless Legs Syndrome: A Systematic Review and Evaluation of Their Face and Construct Validity.

Silvani A, Ghorayeb I, Manconi M, Li Y, Clemens S Neurotherapeutics. 2022; 20(1):154-178.

PMID: 36536233 PMC: 10119375. DOI: 10.1007/s13311-022-01334-4.

Brain-iron deficiency models of restless legs syndrome.

Earley C, Jones B, Ferre S Exp Neurol. 2022; 356:114158.

PMID: 35779614 PMC: 9357217. DOI: 10.1016/j.expneurol.2022.114158.

Iron-deficiency and dopaminergic treatment effects on RLS-Like behaviors of an animal model with the brain iron deficiency pattern of the restless legs syndrome.

Allen R, Earley C, Jones B, Unger E Sleep Med. 2020; 71:141-148.

PMID: 32094092 PMC: 7302997. DOI: 10.1016/j.sleep.2020.01.024.

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