Trophic restoration of the nigrostriatal dopaminergic pathway in long-term carotid body-grafted parkinsonian rats.
We studied the mechanisms underlying long-term functional recovery of hemiparkinsonian rats grafted intrastriatally with carotid body (CB) cell aggregates. Amelioration of their motor syndrome is a result of the trophic actions of these grafts on the remaining ipsilateral substantia nigra neurons rather than of the release of dopamine from the CB grafts. The grafts maintain a stable morphological appearance and differentiated cell phenotype for the duration of the life of the host. Adult CB expresses high levels of glial cell line-derived neurotrophic factor (GDNF) and the multicomponent GDNF receptor complex. These properties may contribute to the trophic actions of the CB transplants on nigrostriatal neurons and to their extraordinary longevity. We show that CB glomus cells, although highly dopaminergic, are protected from dopamine-mediated oxidative damage because of the absence of the high-affinity dopamine transporter. Thus, intrastriatal CB grafts are uniquely suited for long-term delivery of trophic factors capable of promoting restoration of the nigrostriatal pathway.
Toledo-Aral
Juan J
JJ
Laboratorio de Investigaciones Biomédicas, Departamento de Fisiología and Hospital Universitario Virgen del Rocío, Universidad de Sevilla, E-41013 Sevilla, Spain. juanjo@hvr.sas.junta-andalucia.es
Méndez-Ferrer
Simón
S
Pardal
Ricardo
R
Echevarría
Miriam
M
López-Barneo
José
J
D000818:Animals; D001522:Behavior, Animal; D002344:Carotid Body / Q000378:metabolism / Q000637:transplantation*; D002470:Cell Survival; D003342:Corpus Striatum / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009434:Neural Pathways; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D013997:Time Factors
D050483:Dopamine Plasma Membrane Transport Proteins; C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D004298:Dopamine