{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T19:11:10Z","timestamp":1788462670836,"version":"build-2803163510"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS082242"],"award-info":[{"award-number":["NS082242"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA034748"],"award-info":[{"award-number":["DA034748"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Service of the Department of Veterans Affairs","award":["DA034748"],"award-info":[{"award-number":["DA034748"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Study Objectives<\/jats:title>\n                  <jats:p>Brain iron deficiency has been reported to be associated with the restless legs syndrome (RLS). However, 30%\u201350% of RLS patients do not respond to iron therapy, indicating that mechanisms other than brain iron deficiency may also participate in this disease. The striatum is known to be involved in the modulation of motor activity. We speculated that dysfunction of the striatum may induce RLS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Two groups, wild-type (WT) and iron-deficient (ID) rats were used. Each group was divided into two subgroups, control and N-methyl-d-aspartate striatal-lesioned. After baseline recording, striatal-lesioned wild-type (WT-STL) and striatal-lesioned iron-deficient (ID-STL) rats were given pramipexole and thioperamide injections. Iron-deficient and ID-STL rats were then given a standard rodent diet for 4 weeks, and their sleep and motor activity were recorded.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>WT-STL rats showed periodic leg movements (PLM) in wake, an increase in PLM in slow wave sleep (SWS), a decrease in rapid-eye-movement sleep, and a decrease in the daily average duration of episodes in SWS. The sleep\u2013wake pattern and motor activity did not differ between ID and ID-STL rats. Thioperamide or pramipexole injection decreased PLM in sleep and in wake in WT-STL rats and ID-STL rats. Unlike ID rats, whose motor hyperactivity can be reversed by iron replacement, PLM in wake and in sleep in ID-STL rats were not fully corrected by iron treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Lesions of the striatum generate RLS-like activity in rats. Dysfunction of the striatum may be responsible for failure to respond to iron treatment in some human RLS patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/sleep\/zsac110","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T21:21:46Z","timestamp":1652217706000},"source":"Crossref","is-referenced-by-count":7,"title":["Striatal mechanism of the restless legs syndrome"],"prefix":"10.1093","volume":"45","author":[{"given":"Yuan-Yang","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California , Los Angeles, CA , USA"},{"name":"VA Greater Los Angeles HealthCare System , Sepulveda, 16111 Plummer Street, North Hills, CA , USA"},{"name":"Greater Los Angeles Veterans Research and Education Foundation , 11301 Wilshire Blvd, Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kung-Chiao","family":"Hsieh","sequence":"additional","affiliation":[{"name":"VA Greater Los Angeles HealthCare System , Sepulveda, 16111 Plummer Street, North Hills, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keng-Tee","family":"Chew","sequence":"additional","affiliation":[{"name":"VA Greater Los Angeles HealthCare System , Sepulveda, 16111 Plummer Street, North Hills, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darian","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Greater Los Angeles Veterans Research and Education Foundation , 11301 Wilshire Blvd, Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome M","family":"Siegel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California , Los Angeles, CA , USA"},{"name":"VA Greater Los Angeles HealthCare System , Sepulveda, 16111 Plummer Street, North Hills, CA , USA"},{"name":"Brain Research Institute, University of California, Los Angeles , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"issue":"1","key":"2022071108571720700_CIT0001","doi-asserted-by":"crossref","first-page":"10","DOI":"10.13078\/jksrs.12003","article-title":"Reduced cerebral blood perfusion of putamen and insular cortex in patients with idiopathic restless legs syndrome","volume":"9","author":"Joo","year":"2012","journal-title":"J Korea Sleep Res Soc."},{"issue":"1","key":"2022071108571720700_CIT0002","doi-asserted-by":"crossref","first-page":"51","DOI":"10.5665\/sleep.2300","article-title":"Increased synaptic dopamine in the putamen in restless legs syndrome","volume":"36","author":"Earley","year":"2013","journal-title":"Sleep"},{"issue":"2","key":"2022071108571720700_CIT0003","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1007\/PL00007859","article-title":"SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic leg movements in sleep","volume":"249","author":"Michaud","year":"2002","journal-title":"J Neurol."},{"issue":"9","key":"2022071108571720700_CIT0004","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1093\/brain\/awp125","article-title":"Altered dopaminergic profile in the putamen and substantia nigra in restless leg syndrome","volume":"132","author":"Connor","year":"2009","journal-title":"Brain"},{"issue":"1","key":"2022071108571720700_CIT0005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/sleep\/zsaa151","article-title":"Substantia nigra pars reticulata-mediated sleep and motor activity regulation","volume":"44","author":"Lai","year":"2021","journal-title":"Sleep"},{"key":"2022071108571720700_CIT0006","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.sleep.2016.05.001","article-title":"Brain iron deficiency in idiopathic restless legs syndrome measured by quantitative magnetic susceptibility at 7 tesla","volume":"22","author":"Li","year":"2016","journal-title":"Sleep Med."},{"issue":"1","key":"2022071108571720700_CIT0007","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1365-2869.2004.00403.x","article-title":"CSF iron, ferritin and transferrin levels in restless legs syndrome","volume":"14","author":"Mizuno","year":"2005","journal-title":"J Sleep Res."},{"issue":"13","key":"2022071108571720700_CIT0008","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1002\/mds.25576","article-title":"Low brain iron content in idiopathic restless legs syndrome patients detected by phase imaging","volume":"28","author":"Rizzo","year":"2013","journal-title":"Move Disord"},{"issue":"9","key":"2022071108571720700_CIT0009","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.sleep.2011.06.009","article-title":"Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial","volume":"12","author":"Allen","year":"2011","journal-title":"Sleep Med."},{"issue":"3","key":"2022071108571720700_CIT0010","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.sleep.2012.11.001","article-title":"Lower molecular weight intravenous iron dextran for restless legs syndrome","volume":"14","author":"Cho","year":"2013","journal-title":"Sleep Med."},{"issue":"2","key":"2022071108571720700_CIT0011","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/ene.12286","article-title":"Comparison of the efficacies of oral iron and pramipexole for the treatment of restless legs syndrome patients with low serum ferritin","volume":"21","author":"Lee","year":"2014","journal-title":"Eur J Neurol."},{"issue":"11","key":"2022071108571720700_CIT0012","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.sleep.2020.02.027","article-title":"Allen RP. Patient characteristics predicting responses to intravenous ferric carboxymaltose treatment of restless legs syndrome","volume":"75","author":"Park","year":"2020","journal-title":"Sleep Med."},{"issue":"12","key":"2022071108571720700_CIT0013","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1002\/mds.27133","article-title":"Motor hyperactivity of the iron deficient rat\u2014an animal model of restless legs syndrome","volume":"32","author":"Lai","year":"2017","journal-title":"Move Disord."},{"issue":"2","key":"2022071108571720700_CIT0014","first-page":"1","article-title":"Striatal histamine mechanism in the pathogenesis of restless legs syndrome","volume":"43","author":"Lai","year":"2020","journal-title":"Sleep"},{"key":"2022071108571720700_CIT0015","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/j.1365-2141.1975.tb00851.x","article-title":"Brain iron: persistent deficiency following short-term iron deprivation in the young rat","volume":"31","author":"Dallman","year":"1975","journal-title":"Br J Haemotol"},{"issue":"1","key":"2022071108571720700_CIT0016","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0736-5748(86)90019-5","article-title":"Long-term consequence of early iron-deficiency on dopaminergic neurotransmission in rats","volume":"4","author":"Ben-Shachar","year":"1986","journal-title":"Int J Devl Neurosci."},{"issue":"1","key":"2022071108571720700_CIT0017","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/mds.22303","article-title":"Poststroke restless legs syndrome and lesion location: anatomical considerations","volume":"24","author":"Lee","year":"2009","journal-title":"Move Disord."},{"key":"2022071108571720700_CIT0018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fnana.2011.00026","article-title":"Somatotopic organization of the primate basal ganglia","volume":"5","author":"Nambu","year":"2011","journal-title":"Front Neuroanat."},{"issue":"1","key":"2022071108571720700_CIT0019","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/mds.27263","article-title":"Reply: The iron-deficient rat as a model of restless legs syndrome: was anything lost in translation?","volume":"33","author":"Lai","year":"2018","journal-title":"Move Disord."},{"issue":"4","key":"2022071108571720700_CIT0020","doi-asserted-by":"crossref","first-page":"340","DOI":"10.3988\/jcn.2017.13.4.340","article-title":"Abnormal sleep delta rhythm and interregional phase synchrony in patients with restless legs syndrome and their reversal by dopamine agonist treatment","volume":"13","author":"Choi","year":"2017","journal-title":"J Clin Neurol."},{"key":"2022071108571720700_CIT0021","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.clinph.2005.02.004","article-title":"Spectral analysis of sleep EEG in patients with restless legs syndrome","volume":"116","author":"Hornyak","year":"2005","journal-title":"Clin Neurophysiol."},{"issue":"9","key":"2022071108571720700_CIT0022","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/j.clinph.2004.03.032","article-title":"The clinical neurophysiology of the restless legs syndrome and periodic leg movements. Part I: diagnosis, assessment, and characterization","volume":"115","author":"Hening","year":"2004","journal-title":"Clin Neurophysiol."},{"issue":"33","key":"2022071108571720700_CIT0023","doi-asserted-by":"crossref","first-page":"14845","DOI":"10.1073\/pnas.1009874107","article-title":"Distinct subclasses of medium spiny neurons differentially regulate striatal motor behaviors","volume":"107","author":"Bateup","year":"2010","journal-title":"PNAS"},{"issue":"6","key":"2022071108571720700_CIT0024","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1016\/0306-4522(81)90111-1","article-title":"Changes in histamine in the rat striatum following local injection of kainic acid","volume":"12","author":"Sperk","year":"1981","journal-title":"Neuroscience."},{"issue":"8","key":"2022071108571720700_CIT0025","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/S0028-3908(01)00144-7","article-title":"Histamine H3 receptor activation inhibits glutamate release from rat striatal synaptosomes","volume":"41","author":"Molina-Hernandez","year":"2001","journal-title":"Neuropharmacology"},{"key":"2022071108571720700_CIT0026","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.phrs.2017.11.036","article-title":"Functional histamine H3 and adenosine A2A receptor heteromers in recombinant cells and rat striatum","volume":"129","author":"Marquez-Gomez","year":"2018","journal-title":"Pharmacol Res."},{"issue":"2","key":"2022071108571720700_CIT0027","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.neuropharm.2008.05.008","article-title":"Interactions between histamine H3 and dopamine D2 receptors and the implications for striatal function","volume":"55","author":"Ferrada","year":"2008","journal-title":"Neuropharmacology"},{"issue":"10","key":"2022071108571720700_CIT0028","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.nucmedbio.2014.08.002","article-title":"Spinal cord dopamine D2\/D3 receptors: in vivo and ex vivo imaging in the rat using 18F\/11C-fallypride","volume":"41","author":"Kaur","year":"2014","journal-title":"Nucl Med Biol."},{"issue":"1","key":"2022071108571720700_CIT0029","first-page":"1","article-title":"Iron for the treatment of restless legs syndrome","author":"Trotti","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"issue":"6","key":"2022071108571720700_CIT0030","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1093\/sleep\/26.6.735","article-title":"Periodic limb movements in sleep and iron status in children","volume":"26","author":"Simakajornboon","year":"2003","journal-title":"Sleep"},{"issue":"4","key":"2022071108571720700_CIT0031","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1093\/jn\/137.4.1043","article-title":"Gestational and lactational iron deficiency alters the developing striatal metabolome and associated behaviors in young rats","volume":"137","author":"Ward","year":"2007","journal-title":"J Nutrition"}],"container-title":["Sleep"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/sleep\/advance-article-pdf\/doi\/10.1093\/sleep\/zsac110\/43929611\/zsac110.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/sleep\/article-pdf\/45\/7\/zsac110\/44380724\/zsac110.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/sleep\/article-pdf\/45\/7\/zsac110\/44380724\/zsac110.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T08:58:11Z","timestamp":1657529891000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/sleep\/article\/doi\/10.1093\/sleep\/zsac110\/6583453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,10]]},"references-count":31,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,5,10]]},"published-print":{"date-parts":[[2022,7,11]]}},"URL":"https:\/\/doi.org\/10.1093\/sleep\/zsac110","relation":{},"ISSN":["0161-8105","1550-9109"],"issn-type":[{"value":"0161-8105","type":"print"},{"value":"1550-9109","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,7,1]]},"published":{"date-parts":[[2022,5,10]]},"article-number":"zsac110"}}