Locomotion is increased in A11-lesioned mice with iron deprivation: A possible animal model for restless legs syndrome

Shen Qu, Weidong Le, Xiong Zhang, Wenjie Xie, Aijun Zhang, William G. Ondo

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Restless legs syndrome (RLS) is a common neurologic condition involving iron and dopamine systems. We sought to create an animal model consistent with RLS based on current understanding of human pathology. We performed bilateral 6-hydroxydopamine (6-OHDA) lesioning in the A11 nucleus of C57BL/6 mice and deprived a subset of mice from dietary iron to observe whether these manipulations can increase motor activity. Iron levels in serum, brain, and especially spinal cord were significantly decreased after iron deprivation. Interestingly, 6-OHDA lesioning appeared to further reduce CNS iron stores. Pathologic examination demonstrated a 94% reduction in A11 tyrosine hydroxylase staining cells in mice injected with 6-OHDA but minimal effects on other areas. Locomotor activities were significantly increased in both the mice that were iron deprived and the A11-lesioned mice compared with controls. The combination of iron deprivation and A11 lesions further significantly augmented activity. Additionally, the mice in the combined iron-deprived and lesioned group were more aggressive. The increased activity in A11-lesioned mice with or without iron deprivation was normalized after treatment with the D2/D3 agonist ropinirole, as is seen in human RLS but was worsened by the D1 agonist SKF38393. This model could be consistent with human RLS, attention deficit hyperactivity disorder, or akathisia.

Original languageEnglish (US)
Pages (from-to)383-388
Number of pages6
JournalJournal of Neuropathology and Experimental Neurology
Volume66
Issue number5
DOIs
StatePublished - May 2007

Keywords

  • Animal models
  • Dopamine
  • Iron
  • Restless legs syndrome

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

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