Adenosine receptors as markers of brain iron deficiency: Implications for Restless Legs Syndrome

César Quiroz, Seema Gulyani, Wan Ruiqian, Jordi Bonaventura, Roy Cutler, Virginia Pearson, Richard P. Allen, Christopher J. Earley, Mark P. Mattson, Sergi Ferré

Research output: Research - peer-reviewArticle

Abstract

Deficits of sensorimotor integration with periodic limb movements during sleep (PLMS) and hyperarousal and sleep disturbances in Restless Legs Syndrome (RLS) constitute two pathophysiologically distinct but interrelated clinical phenomena, which seem to depend mostly on alterations in dopaminergic and glutamatergic neurotransmission, respectively. Brain iron deficiency is considered as a main pathogenetic mechanism in RLS. Rodents with brain iron deficiency represent a valuable pathophysiological model of RLS, although they do not display motor disturbances. Nevertheless, they develop the main neurochemical dopaminergic changes found in RLS, such as decrease in striatal dopamine D2 receptor density. On the other hand, brain iron deficient mice exhibit the characteristic pattern of hyperarousal in RLS, providing a tool to find the link between brain iron deficiency and sleep disturbances in RLS. The present study provides evidence for a role of the endogenous sleep-promoting factor adenosine. Three different experimental preparations, long-term (22 weeks) severe or moderate iron-deficient (ID) diets (3- or 7-ppm iron diet) in mice and short-term (3 weeks) severe ID diet (3-ppm iron diet) in rats, demonstrated a significant downregulation (Western blotting in mouse and radioligand binding saturation experiments in rat brain tissue) of adenosine A1 receptors (A1R) in the cortex and striatum, concomitant to striatal D2R downregulation. On the other hand, the previously reported upregulation of adenosine A2A receptors (A2AR) was only observed with severe ID in both mice and rats. The results suggest a key role for A1R downregulation in the PLMS and hyperarousal in RLS.

LanguageEnglish (US)
Pages160-168
Number of pages9
JournalNeuropharmacology
Volume111
DOIs
StatePublished - Dec 1 2016

Fingerprint

Restless Legs Syndrome
Purinergic P1 Receptors
Iron
Brain
Sleep
Diet
Adenosine
Down-Regulation
Corpus Striatum
Extremities
Synaptic Transmission
Rodentia
Dopamine
Up-Regulation
Western Blotting

Keywords

  • Adenosine A receptor
  • Adenosine A receptor
  • Brain iron deficiency
  • Dopamine D receptor
  • Restless Legs Syndrome

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Quiroz, C., Gulyani, S., Ruiqian, W., Bonaventura, J., Cutler, R., Pearson, V., ... Ferré, S. (2016). Adenosine receptors as markers of brain iron deficiency: Implications for Restless Legs Syndrome. Neuropharmacology, 111, 160-168. DOI: 10.1016/j.neuropharm.2016.09.002

Adenosine receptors as markers of brain iron deficiency : Implications for Restless Legs Syndrome. / Quiroz, César; Gulyani, Seema; Ruiqian, Wan; Bonaventura, Jordi; Cutler, Roy; Pearson, Virginia; Allen, Richard P.; Earley, Christopher J.; Mattson, Mark P.; Ferré, Sergi.

In: Neuropharmacology, Vol. 111, 01.12.2016, p. 160-168.

Research output: Research - peer-reviewArticle

Quiroz, C, Gulyani, S, Ruiqian, W, Bonaventura, J, Cutler, R, Pearson, V, Allen, RP, Earley, CJ, Mattson, MP & Ferré, S 2016, 'Adenosine receptors as markers of brain iron deficiency: Implications for Restless Legs Syndrome' Neuropharmacology, vol 111, pp. 160-168. DOI: 10.1016/j.neuropharm.2016.09.002
Quiroz C, Gulyani S, Ruiqian W, Bonaventura J, Cutler R, Pearson V et al. Adenosine receptors as markers of brain iron deficiency: Implications for Restless Legs Syndrome. Neuropharmacology. 2016 Dec 1;111:160-168. Available from, DOI: 10.1016/j.neuropharm.2016.09.002
Quiroz, César ; Gulyani, Seema ; Ruiqian, Wan ; Bonaventura, Jordi ; Cutler, Roy ; Pearson, Virginia ; Allen, Richard P. ; Earley, Christopher J. ; Mattson, Mark P. ; Ferré, Sergi. / Adenosine receptors as markers of brain iron deficiency : Implications for Restless Legs Syndrome. In: Neuropharmacology. 2016 ; Vol. 111. pp. 160-168
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