ArticleBehavioural brain research2019
Hyperactivity, dopaminergic abnormalities, iron deficiency and anemia in an in vivo opioid receptors knockout mouse: Implications for the restless legs syndrome.
Article in Behavioural brain research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- 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 · 2023Pooled it
- Effect of dairy products fortified with vitamin dBMC women's health · 2024Trial
- Restless legs syndrome in children with celiac disease: associations with vitamin D and iron deficiency and the role of gluten-free diet adherence.BMC pediatrics · 2026Article
- Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome.Brain : a journal of neurology · 2024Article
- Vitamin D and Restless Legs Syndrome: A Review of Current Literature.Tremor and other hyperkinetic movements (New York, N.Y.) · 2023Review
- Circadian rhythm in restless legs syndrome.Frontiers in neurology · 2023Review
- Exploring the role of the endogenous opiate system in the pathogenesis of anemia in an opiate receptor knock-out model of Restless Legs Syndrome.Medical hypotheses · 2022Article
- Consensus guidelines on the construct validity of rodent models of restless legs syndrome.Disease models & mechanisms · 2022Article
- Deficiency of Meis1, a transcriptional regulator, in mice and worms: Neurochemical and behavioral characterizations with implications in the restless legs syndrome.Journal of neurochemistry · 2020Article
- Gamma Aminobutyric Acid Increases Absorption of Glycine-Bound Iron in Mice with Iron Deficiency Anemia.Biological trace element research · 2020Article
- The Role of BTBD9 in the Cerebellum, Sleep-like Behaviors and the Restless Legs Syndrome.Neuroscience · 2020Article
- Mu opioid receptor knockout mouse: Phenotypes with implications on restless legs syndrome.Journal of neuroscience research · 2020Article
- BTBD9 and dopaminergic dysfunction in the pathogenesis of restless legs syndrome.Brain structure & function · 2020Article
- The role of BTBD9 in the cerebral cortex and the pathogenesis of restless legs syndrome.Experimental neurology · 2020Article
- Association of Rare Genetic Variants in Opioid Receptors with Tourette Syndrome.Tremor and other hyperkinetic movements (New York, N.Y.) · 2019Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Previous studies have uncovered a potential role of the opioid system in iron hemostasis and dopamine metabolism. Abnormalities in both of these systems have been noted in human RLS. Autopsy studies of human RLS have shown an endogenous opioid deficiency in the thalamus. Opioids, particularly prolonged-release oxycodone/naloxone, have been approved in Europe to be a second-line therapy for severe restless legs syndrome (RLS). To study the role of opioid receptors in the pathogenesis of RLS, we used a triple knockout (KO) mouse strain that lack mu, delta, and kappa opioid receptors and explored the behavioral and biochemical parameters relevant to RLS. The triple KO mice showed hyperactivity and a trend of increased probability of waking during the rest period (day) akin to that in human RLS (night). Surprisingly, triple KO mice also exhibit decreased serum iron concentration, evidence of anemia, a significant dysfunction in dopamine metabolism akin to that noted in human RLS, as well as an increased latency in response to thermal stimuli. To our knowledge, this is the first study to demonstrate that the endogenous opioid system may play a role in iron metabolism and subsequently in the pathogenesis of anemia. It is also the first study showing that opioid receptors are involved in the production of motor restlessness with a circadian predominance. Our findings support the role of endogenous opioids in the pathogenesis of RLS, and the triple KO mice can be used to understand the relationship between iron deficiency, anemia, dopaminergic dysfunction, and RLS.
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Registered trials
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.