title: Neonatal ablation of the nigrostriatal dopamine pathway does not influence limb development in rats.
abstract: Hemiparkinson-hemiatrophy syndrome (HP-HA) is associated with skeletal hemiatrophy and the later development of parkinsonism. It is generally assumed that this phenotype is due to the combination of dysfunction of the basal ganglia (e.g., substantia nigra compacta and/or other related structures), causing parkinsonism, and of other areas (e.g., cerebral cortex), causing hemiatrophy. The occurrence of asymmetry of limb size in a patient with very asymmetric involvement of dopa-responsive dystonia encouraged Greene et al. (2000, Mov. Disord. 15: 537-541) to propose that lifelong deficits in nigrostriatal dopamine could account for limb asymmetry in HP-HA. The purpose of this study was to determine whether skeletal hemiatrophy could be produced in rats by unilateral, neonatal ablation of the nigrostriatal dopamine pathway. Infusion of 6-hydroxydopamine into the striatum of rat neonates resulted in loss of dopamine neurons in the ipsilateral substantia nigra, reduced striatal dopamine levels, and stimulant-induced motor asymmetry. Saline infusions neither altered the number of dopamine neurons nor produced behavioral changes. Both groups incurred discrete lesions of the ipsilateral motor cortex surrounding the infusion site and atrophy of the corresponding cerebral peduncle. Cortical, but not nigrostriatal, lesions were associated with significant atrophy of ipsilateral femora, humeri, and innominate bones, as assessed radiographically. Skeletal hemiatrophy was not observed in naive animals or in experimental animals that did not exhibit corticospinal abnormalities. The results of this study indicate that early skeletal development in rats is not affected by loss of nigrostriatal dopamine per se, but is markedly attenuated by corticospinal lesions sustained during the neonatal period.
authors.affiliation: Division of Neurosurgery, University of Toronto, Toronto, Ontario, M5T 2S8, Canada.
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Hebb
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fletcher
authors.forename: John W
authors.initials: JW
authors.lastname: Chambers
authors.forename: Andres M
authors.initials: AM
authors.lastname: Lozano
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D005121:Extremities / Q000254:growth & development* / Q000473:pathology; D007867:Leg Bones / Q000000981:diagnostic imaging / Q000254:growth & development / Q000473:pathology; D007870:Leg Length Inequality / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*; D008636:Mesencephalon / Q000473:pathology; D009044:Motor Cortex / Q000473:pathology; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D011712:Pyramidal Tracts / Q000473:pathology; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
chemical_list: D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine