Spinal cord dopamine receptor expression and function in mice with 6-OHDA lesion of the A11 nucleus and dietary iron deprivation.
It is suggested that dysfunction of the diencephalospinal dopaminergic (DAergic) pathway may cause restless legs syndrome. We examined the mRNA and protein levels as well as DA receptor subtypes function within the lumbar spinal cord of an RLS animal model. C57BL/6 male mice with or without iron deprivation were lesioned with 6-hydroxydopamine (6-OHDA) in the bilateral A11 nuclei. Locomotor behaviors were observed. DA concentration, mRNA, and protein levels of D1, D2, and D3 receptors in the lumbar spinal cords were analyzed, and the specific binding of D1, D2, and D3 receptors was determined using [(3)H]SCH23390, [(3)H]Spiperone, and [(3)H]PD128907 radioligands respectively. The behavioral tests showed that the locomotor activities were increased significantly in the mice treated with iron-deficiency (ID) diet and 6-OHDA lesions, which were reversed by the D2/D3 agonist ropinirole. DA in the spinal cord was decreased significantly by 6-OHDA lesioning in A11. D2/D3 mRNA and protein levels as well as their binding capacity in the spinal cord were decreased significantly by 6-OHDA lesions. ID with 6-OHDA lesions produced a synergistic greater decrease of D2 binding. Although ID increased D1 mRNA and protein expression in the spinal cord, it did not significantly change D1 receptor binding. The present study suggests that ID and 6-OHDA lesions in A11 nuclei differentially altered the D1, D2, and D3 receptors expression and binding capacity in the lumbar spinal cord of RLS animal model, which was accompanied by changes in locomotor activities.
Zhao
Hongru
H
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.
Zhu
Wen
W
Pan
Tianhong
T
Xie
Wenjie
W
Zhang
Aijun
A
Ondo
William G
WG
Le
Weidong
W
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D003714:Denervation; D004195:Disease Models, Animal; D004298:Dopamine / Q000096:biosynthesis*; D004302:Dorsomedial Hypothalamic Nucleus / Q000378:metabolism* / Q000503:physiopathology; D004525:Efferent Pathways / Q000378:metabolism* / Q000503:physiopathology; D005526:Food, Formulated; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism*; D012148:Restless Legs Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology
D019266:Iron, Dietary; D009498:Neurotoxins; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D016627:Oxidopamine; D004298:Dopamine