Document Detail

Modification of the number and phenotype of striatal dopaminergic cells by carotid body graft.
MedLine Citation:
PMID:  17439984     Owner:  NLM     Status:  MEDLINE    
In non-human primates, striatal tyrosine hydroxylase-immunoreactive (TH-ir) cells are increased in number after dopamine depletion and in response to trophic factor delivery. As carotid body cells contain the dopaminotrophic glial cell line-derived neurotrophic factor (GDNF), we evaluated the number, morphology and neurochemistry of these TH-ir cells, in the anterior and posterior striatum of five monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which received a graft of carotid body cell aggregates (CBCA) (n = 3) or sham surgery (n = 2), and six MPTP-monkeys that were sacrificed 6 months and 3 years after the last MPTP dose [MPTP I (n = 3) and MPTP II (n = 3), respectively]. Three intact monkeys served as controls. A disability rating scale was used for the assessment of parkinsonism in all lesioned animals, both before and after surgery. For the neurochemical examination, tissue sections were double-labelled with antibodies to TH, dopamine transporter, dopa decarboxylase-67, vesicular monoamine transporter 2, glutamic acid decarboxylase -67, calbindin, parvalbumin, calretinin, neuronal nitric oxide synthase and GDNF. Only animals receiving CBCA graft showed a moderate but significant recovery of parkinsonism that persisted 12 months after the graft. The grafted striatum contained the greatest TH-ir cell density (120.4 +/- 10.3 cells/100 mm2), while the control striatum displayed the lowest (15.4 +/- 6.8 cells/100 mm2), and MPTP I, MPTP II and sham-operated monkeys showed a similar intermediate value (66.1 +/- 6.2, 58.3 +/- 17.2 and 57.7 +/- 7.0 cells/100 mm2, respectively). In addition, in the post-commissural striatum, only CBCA graft induced a significant increase in the TH-ir cell density compared to control animals (47.9 +/- 15.9 and 7.9 +/- 3.2, respectively). Phenotypically, TH-ir cells were striatal dopaminergic interneurons. However, in the grafted animals, the phenotype was different from that in control, MPTP and sham-operated monkeys, with the appearance of TH/GDNF-ir cells and the emergence of two TH-ir subpopulations of different size as the two main differentiating features. Our data confirm and extend previous studies demonstrating that striatal CBCA grafts produce a long-lasting motor recovery of MPTP-monkeys along with an increase in the number and phenotype changes of the striatal TH-ir interneurons, probably by the action of the trophic factors contained in carotid body cells. The increased number of striatal TH-ir cells observed in the grafted striatum may contribute to the improvement of parkinsonism observed after the graft.
W San Sebastián; J Guillén; M Manrique; S Belzunegui; E Ciordia; A Izal-Azcárate; P Garrido-Gil; M Vázquez-Claverie; M R Luquin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-17
Journal Detail:
Title:  Brain : a journal of neurology     Volume:  130     ISSN:  1460-2156     ISO Abbreviation:  Brain     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-05-02     Completed Date:  2007-05-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372537     Medline TA:  Brain     Country:  England    
Other Details:
Languages:  eng     Pagination:  1306-16     Citation Subset:  AIM; IM    
Laboratory of Regenerative Therapy, Center for Applied Medical Research, University of Navarra, Avenida de Pío XII, 55, Pamplona, Navarra, Spain.
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MeSH Terms
Biological Markers / analysis
Carotid Body / transplantation*
Cell Count
Cell Differentiation
Corpus Striatum / metabolism*,  pathology*
Dopamine / metabolism*
Fluorescent Antibody Technique, Indirect
Glial Cell Line-Derived Neurotrophic Factor / analysis
Macaca fascicularis
Models, Animal
Parkinsonian Disorders / metabolism,  pathology,  surgery*
Tyrosine 3-Monooxygenase / analysis
Reg. No./Substance:
0/Biological Markers; 0/Glial Cell Line-Derived Neurotrophic Factor; 28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; EC 3-Monooxygenase

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