Abstract
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 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society
Highlights
Restless legs syndrome (RLS) is a sensory-motor disorRdeers1t,l2escshlaergascstyernidzerodmbey(RunLpSl)eaissaansteannsodryp-aminoftuolr sdeins-osartdieorn1s,2 acnhdaraiscteursiuzeadllybyacuconmplpeaasnainedt abnyd ppaariensftuhlessieans-. sTahtieosne suanncodmifsorutasubalellyseancscaotimonpsanoicecdurbyduprainrgestrheesstiaosr
We found that ID rats exhibit sleep fragmentation, motor hyperactivity, PLM in quiet wake, and an increase in PLM in sleep, signs resembling those in human RLS patients
We found that iron therapy improved PLM in quiet wake and in sleep, hematocrit levels, and sleep quality
Summary
Restless legs syndrome (RLS) is a sensory-motor disorRdeers1t,l2escshlaergascstyernidzerodmbey(RunLpSl)eaissaansteannsodryp-aminoftuolr sdeins-osartdieorn1s,2 acnhdaraiscteursiuzeadllybyacuconmplpeaasnainedt abnyd ppaariensftuhlessieans-. sTahtieosne suanncodmifsorutasubalellyseancscaotimonpsanoicecdurbyduprainrgestrheesstiaosr. HHooww-eevveerr,, ppeerriiooddiicc lleegg mmoovveemmeennttss ((PPLLMMss)),, aann oobbjjeeccttiivvee mmoottoorr eevveenntt,, ccaann bbee rreeccoorrddeedd iinn aanniimmaallss. PPLLMMss iinn quietwwakaekeisis cocommmmoonn inin RRLLSS ppaattiieennttss..1111,,1122. LAI ET AL substantia nigra and abnormal sleep architecture have been reported in ID rats and mice, respectively.[15,16] motor activity in quiet wake and in sleep, a key element of restless legs syndrome, has not been studied in ID animals. We examine whether ID rats have abnormal sleep patterns and motor activity, using video and polysomnographic recording techniques. Abnormal striatal dopamine transmission — increased, decreased, or unchanged dopamine transporter (DAT) level — has been reported in idiopathic RLS patients.[17,18,19] we have measured striatal DAT levels in ID rats compared with control rats, using the Western blot technique
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