Locomotion is increased in a11-lesioned mice with iron deprivation: a possible animal model for restless legs syndrome.
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.
Qu
Shen
S
Departments of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.
Le
Weidong
W
Zhang
Xiong
X
Xie
Wenjie
W
Zhang
Aijun
A
Ondo
William G
WG
D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D004027:Diencephalon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007501:Iron / Q000097:blood; D000090463:Iron Deficiencies; D008124:Locomotion / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016627:Oxidopamine; D012148:Restless Legs Syndrome; D013116:Spinal Cord / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018491:Dopamine Agonists; D007211:Indoles; C046649:ropinirole; D016627:Oxidopamine; D007501:Iron; D014446:Tyrosine 3-Monooxygenase