Evidence map›Paper›PMID 35779614›Full record

ReviewExperimental neurology2022

Brain-iron deficiency models of restless legs syndrome.

Christopher J Earley, Byron C Jones, Sergi Ferré

Open access · greenAbstract readReview
In one paragraph

Review in Experimental neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
6.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

  1. Putative Animal Models of Restless Legs Syndrome: A Systematic Review and Evaluation of Their Face and Construct Validity.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Pooled it
  2. Trial
  3. Article
  4. Altered iron metabolism and iron therapy in restless legs syndrome.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  5. Dopaminergic hypersensitivity of the opioid-responsive striatal-entopeduncular pathway in a rodent model of restless legs syndrome.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Christopher J EarleyDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: cearley@jhmi.edu.
Byron C JonesDepartment of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA.
Sergi FerréIntegrative Neurobiology Section, National Institutes of Health/National Institute on Drug Abuse, Baltimore, MD, USA.
University of Tennessee Health Science Center · US

Funding

Neurotransmitter Receptor Heteromers in the Striatal Spine ModuleZIADA000493 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI FERRE, SERGI · 2009 to 2025
$35.6M
THE IRON-DOPAMINE CONNECTIONP01AG021190 · NIA · JOHNS HOPKINS UNIVERSITY · PI EARLEY, CHRISTOPHER J · 2004 to 2009
$10.0M
Dopamine and Iron in Restless Legs SyndromeR01NS042857 · NINDS · JOHNS HOPKINS UNIVERSITY · PI EARLEY, CHRISTOPHER J · 2003 to 2006
$2.1M
Response to Iron Treatment for Restless Leg SyndromeR01AG020287 · NIA · JOHNS HOPKINS UNIVERSITY · PI EARLEY, CHRISTOPHER J · 2002 to 2004
$1.5M
DOPAMINERGIC FUNCTION IN RESTLESS LEGS SYNDROMER01NS038704 · NINDS · JOHNS HOPKINS UNIVERSITY · PI EARLEY, CHRISTOPHER J · 1999 to 2001
$621k
NIA NIH HHS P01 AG021190NIA NIH HHS R01 AG020287NINDS NIH HHS R01 NS038704NINDS NIH HHS R01 NS042857
6 · The paper itself

Abstract

Restless legs syndrome (RLS) is a common sensorimotor disorder for which two main pathological elements are fairly well accepted: Brain iron deficiency (BID) and an altered dopaminergic system. The ability to better understand the causal and consequential factors related to these two pathological elements, would hopefully lead to the development of better therapeutic strategies for treating, if not curing, this disease. The current understanding of the relationship between these two elements is that BID leads to some alterations in neurotransmitters and subsequent changes in the dopaminergic system. Therefore, rodent models based on diet-induced BID, provide a biological substrate to understand the consequences of BID on dopaminergic pathway and on alternative pathways that may be involved. In this review, we present the current research on dopaminergic changes found in RLS subjects and compare that to what is seen in the BID rodent model to provide a validation of the BID rodent model. We also demonstrate the ability of the BID model to predict changes in other neurotransmitter systems and how that has led to new treatment options. Finally, we will present arguments for the utility of recombinant inbred mouse strains that demonstrate natural variation in brain iron, to explore the genetic basis of altered brain iron homeostasis as a model to understand why in idiopathic RLS there can exist a BID despite normal peripheral iron store. This review is the first to draw on 25 years of human and basic research into the pathophysiology of RLS to provide strong supportive data as to the validity of BID model as an important translational model of the disease. As we will demonstrate here, not only does the BID model closely and accurately mimic what we see in the dopaminergic system of RLS, it is the first model to identify alternative systems from which new treatments have recently been developed.

Indexed as

Iron DeficienciesRestless Legs SyndromeAnimalsBrainDopamineHumansIronMiceDopamineIronGeneticsIron deficiencyNeurotransmitter systemsRestless legs syndromeRodent modelsTranslational research

Identifiers

PMID35779614
PMCPMC9357217
OpenAlexW4283768762

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.