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 ra...

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Bibliographic Details
Published in:The Journal of neuroscience 2003-01, Vol.23 (1), p.141-148
Main Authors: Toledo-Aral, Juan J, Mendez-Ferrer, Simon, Pardal, Ricardo, Echevarria, Miriam, Lopez-Barneo, Jose
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal
Carotid Body - metabolism
Carotid Body - transplantation
Cell Survival
Corpus Striatum - cytology
Corpus Striatum - pathology
Corpus Striatum - physiology
Dopamine - metabolism
Dopamine Plasma Membrane Transport Proteins
Female
Glial Cell Line-Derived Neurotrophic Factor
Membrane Glycoproteins
Membrane Transport Proteins - metabolism
Mice
Mice, Inbred C57BL
Nerve Growth Factors - metabolism
Nerve Tissue Proteins
Neural Pathways
Neurons - drug effects
Neurons - metabolism
Neurotoxins - pharmacology
Parkinson Disease - metabolism
Parkinson Disease - pathology
Parkinson Disease - therapy
Rats
Rats, Wistar
Substantia Nigra - cytology
Substantia Nigra - pathology
Substantia Nigra - physiology
Time Factors
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.23-01-00141.2003