Motor hyperactivity of the iron-deficient rat - an animal model of restless legs syndrome.

TitleMotor hyperactivity of the iron-deficient rat - an animal model of restless legs syndrome.
Publication TypeJournal Article
Year of Publication2017
AuthorsLai Y-Y, Cheng Y-H, Hsieh K-C, Nguyen D, Chew K-T, Ramanathan L, Siegel JM
JournalMovement Disorders
Date Published2017 Dec
KeywordsAnalysis of Variance, Animals, Antiparkinson Agents, Benzothiazoles, Corpus Striatum, Disease Models, Animal, Dopamine Plasma Membrane Transport Proteins, Dose-Response Relationship, Drug, Electroencephalography, Electromyography, Hematocrit, Hyperkinesis, Iron, Iron Metabolism Disorders, Polysomnography, Pramipexole, Rats, Rats, Sprague-Dawley, Restless Legs Syndrome

BACKGROUND: Abnormal 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.

METHODS: After 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.

RESULTS: Iron-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.

CONCLUSIONS: The iron-deficient rat is a useful animal model of iron-deficient anemic restless legs syndrome. © 2017 International Parkinson and Movement Disorder Society.

Alternate JournalMov. Disord.
PubMed ID28843017
PubMed Central IDPMC5759344
Grant ListI01 BX001753 / BX / BLRD VA / United States
R01 DA034748 / DA / NIDA NIH HHS / United States
R01 NS082242 / NS / NINDS NIH HHS / United States