TY - JOUR
T1 - Locomotion is increased in A11-lesioned mice with iron deprivation
T2 - A possible animal model for restless legs syndrome
AU - Qu, Shen
AU - Le, Weidong
AU - Zhang, Xiong
AU - Xie, Wenjie
AU - Zhang, Aijun
AU - Ondo, William G.
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
KW - Animal models
KW - Dopamine
KW - Iron
KW - Restless legs syndrome
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U2 - 10.1097/nen.0b013e3180517b5f
DO - 10.1097/nen.0b013e3180517b5f
M3 - Article
C2 - 17483695
AN - SCOPUS:34247882793
SN - 0022-3069
VL - 66
SP - 383
EP - 388
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 5
ER -