Document Detail

Differential effects of glial cell line-derived neurotrophic factor on A9 and A10 dopamine neuron survival in vitro.
MedLine Citation:
PMID:  17583436     Owner:  NLM     Status:  MEDLINE    
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.
L Borgal; M Hong; D Sadi; I Mendez
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-20
Journal Detail:
Title:  Neuroscience     Volume:  147     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-03     Completed Date:  2007-10-19     Revised Date:  2007-11-23    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  712-9     Citation Subset:  IM    
Cell Restoration Laboratory, Brain Repair Centre, Dalhousie University, Halifax, NS, Canada.
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MeSH Terms
Calcium-Binding Protein, Vitamin D-Dependent / metabolism
Cell Count / methods
Cell Differentiation / drug effects*
Cells, Cultured
Dopamine / metabolism*
Embryo, Mammalian
Embryo, Nonmammalian
G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism
Glial Cell Line-Derived Neurotrophic Factor / pharmacology*
Neurons / drug effects*
Substantia Nigra / cytology*
Tyrosine 3-Monooxygenase / metabolism
Ventral Tegmental Area / cytology*
Reg. No./Substance:
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 3-Monooxygenase

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