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

NEUROPHARMACOLOGY

卷:111

Article

Quiroz, Cesar¹  Gulyani, Seema²  Ruiqian, Wan²  Bonaventura, Jordi¹  Cutler, Roy²  Pearson, Virginia³  Allen, Richard R.³  Earley, Christopher J.³  Mattson, Mark P.²  Ferre, Sergi¹ 

[1] NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA

[2] NIA, Lab Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA

[3] Johns Hopkins Sch Med, Dept Neurol, Ctr Restless Legs Study, Baltimore, MD 21224 USA

关键词: Restless Legs Syndrome;    Brain iron deficiency;    Adenosine A(1) receptor;    Adenosine A(2A) receptor;    Dopamine D-2 receptor;   

DOI  :  10.1016/j.neuropharm.2016.09.002

来源: Elsevier

【 摘 要 】

Deficits of sensorimotor integration with periodic limb movements during sleep (PLMS) and hyper arousal 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 D-2 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 radio-ligand binding saturation experiments in rat brain tissue) of adenosine A(1) receptors (MR) in the cortex and striatum, concomitant to striatal D2R downregulation. On the other hand, the previously reported upregulation of adenosine A(2A) receptors (A2AR) was only observed with severe ID in both mice and rats. The results suggest a key role for MR downregulation in the PLMS and hyperarousal in RLS. Published by Elsevier Ltd.

【 授权许可】

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