Aerobic exercise as a non-pharmacological approach to restless legs syndrome: Evidence from an ID-induced model.

INTRODUCTION: Restless Legs Syndrome (RLS) is a sleep disorder characterized by the urge to move, primarily affecting the legs, especially during rest and at night, leading to difficulty or inability to initiate and maintain sleep. Exercise is a strategy that can improve symptoms; however, it remains underexplored. AIM: In this context, the aim of this study was to evaluate the effects of chronic aerobic exercise on sleep and on dopamine, adenosine, and glutamate systems in an iron-deficient animal model of Restless Legs Syndrome (RLS). METHODS: Male Wistar rats were assigned to a control group (CTRL, standard diet), an iron-deficient group (ID, iron-restricted diet), an exercised control group (CTRLEX), and an exercised iron-deficient group (IDEX). After 9 weeks of diet, the exercise groups underwent treadmill running for four weeks, followed by sleep (electrocorticographic and electromyographic activity) and molecular (western blotting, PCR and ELISA) analyses. KEY FINDINGS: The ID group showed impairments in all expected sleep parameters associated with RLS, including reduced total sleep time and sleep efficiency, along with increased wakefulness, arousals, and limb movements compared with CTRL. In contrast, the IDEX group showed improvements in all these parameters compared with ID. Additionally, exercise increased dopamine transporter (DAT) and adenosine A1 receptor (A1R) levels, which may underlie the observed symptom improvements. SIGNIFICANCE: These findings highlight the potential of physical exercise as a non-pharmacological treatment for sleep problems associated with RLS and provide insights into possible molecular pathways underlying these improvements.