• Yuan-Yang Lai, Yu-Hsuan Cheng, Kung-Chiao Hsieh, Darian Nguyen, Keng-Tee Chew, Lalini Ramanathan, and Jerome M Siegel.
• Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA.
• Mov. Disord. 2017 Dec 1; 32 (12): 1687-1693.

BackgroundAbnormal striatal dopamine transmission has been hypothesized to cause restless legs syndrome. Dopaminergic drugs are commonly used to treat restless legs syndrome. However, they cause adverse effects with long-term use. An animal model would allow the systematic testing of potential therapeutic drugs. A high prevalence of restless legs syndrome has been reported in iron-deficient anemic patients. We hypothesized that the iron-deficient animal would exhibit signs similar to those in restless legs syndrome patients.MethodsAfter baseline polysomnographic recordings, iron-deficient rats received pramipexole injection. Then, iron-deficient rats were fed a standard rodent diet, and polysomnographic recording were performed for 2 days each week for 4 weeks.ResultsIron-deficient rats have low hematocrit levels and show signs of restless legs syndrome: sleep fragmentation and periodic leg movements in wake and in slow-wave sleep. Iron-deficient rats had a positive response to pramipexole treatment. After the iron-deficient rats were fed the standard rodent diet, hematocrit returned to normal levels, and sleep quality improved, with increased average duration of wake and slow-wave sleep episodes. Periodic leg movements decreased during both waking and sleep. Hematocrit levels positively correlated with the average duration of episodes in wake and in slow-wave sleep and negatively correlated with periodic leg movements in wake and in sleep. Western blot analysis showed that striatal dopamine transporter levels were higher in iron-deficient rats.ConclusionsThe iron-deficient rat is a useful animal model of iron-deficient anemic restless legs syndrome. © 2017 International Parkinson and Movement Disorder Society.© 2017 International Parkinson and Movement Disorder Society.

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