| Differential effects of glial cell line-derived neurotrophic factor on A9 and A10 dopamine neuron survival in vitro. | |
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MedLine Citation:
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PMID: 17583436 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glial cell-line derived neurotrophic factor (GDNF) enhances dopamine (DA) cell survival and fiber outgrowth, and may be beneficial in enhancing cell restorative strategies for Parkinson's disease (PD). However, GDNF may have different roles for transplanted DA cell sub-types. The present in vitro study investigated the effect of GDNF on the survival of rat DA cells displaying a phenotype consistent with either the substantia nigra [A9 cells immunopositive for tyrosine hydroxylase (TH) and G-protein-gated inwardly rectifying potassium channel subunit 2 (GIRK2)] or with the ventral tegmental area [A10 cells immunopositive for TH and calbindin]. It was found that a single exposure of GDNF enhanced the number of DA cells of an A9 phenotype, without affecting DA cells of an A10 phenotype. Conversely, repeated GDNF exposure did not alter the survival of A9 phenotypic cells, but doubled the percentage of A10 cells. It was concluded that GDNF administration may affect dopaminergic cells differently depending on time and degree of GDNF exposure. For cell transplantation in PD, long-term GDNF administration may result in detrimental effects for transplanted A9 TH+ cells as this may introduce competition with A10 TH+ cells for survival and fiber outgrowth into the host striatum. These results may have important implications for clinical neural transplantation in PD. |
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Authors:
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L Borgal; M Hong; D Sadi; I Mendez |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-06-20 |
Journal Detail:
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Title: Neuroscience Volume: 147 ISSN: 0306-4522 ISO Abbreviation: Neuroscience Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-07-03 Completed Date: 2007-10-19 Revised Date: 2007-11-23 |
Medline Journal Info:
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Nlm Unique ID: 7605074 Medline TA: Neuroscience Country: United States |
Other Details:
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Languages: eng Pagination: 712-9 Citation Subset: IM |
Affiliation:
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Cell Restoration Laboratory, Brain Repair Centre, Dalhousie University, Halifax, NS, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium-Binding Protein, Vitamin D-Dependent / metabolism Cell Count / methods Cell Differentiation / drug effects* Cells, Cultured Dopamine / metabolism* Embryo, Mammalian Embryo, Nonmammalian Female G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism Glial Cell Line-Derived Neurotrophic Factor / pharmacology* Neurons / drug effects* Pregnancy Rats Substantia Nigra / cytology* Tyrosine 3-Monooxygenase / metabolism Ventral Tegmental Area / cytology* |
| Chemical | |
Reg. No./Substance:
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0/Calcium-Binding Protein, Vitamin D-Dependent; 0/G Protein-Coupled Inwardly-Rectifying Potassium Channels; 0/Glial Cell Line-Derived Neurotrophic Factor; 0/calbindin; EC 1.14.16.2/Tyrosine 3-Monooxygenase |
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