Enhanced GDNF expression in dopaminergic cells of monkeys grafted with carotid body cell aggregates.

Abstract

Striatal carotid body cell aggregates (CBCA) grafts improve parkinsonism in animals and patients with Parkinson's disease. As CB cells contain trophic factors, we investigated the long-term effect of striatal CBCA grafts on nigrostriatal dopaminergic cells in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys receiving unilateral (UL-grafted group, n=4) or bilateral (BL-grafted group, n=3) CBCA autotransplant. Two MPTP monkeys were sham-operated receiving only Tyrode. For histological analysis, we also included 3 MPTP-untreated and 3 intact animals. Brain [18]F-luorodopa ((18)F-DOPA)-positron emission tomography (PET) scans were performed to assess dopaminergic function in vivo at baseline, 6 and 12months after surgery. The number of nigral dopaminergic cells was assessed in UL-grafted animals, and the number of dopaminergic cells expressing glial cell line-derived neurotrophic factor (GDNF) in all groups. After 1 year, animals showed a significant recovery of the parkinsonism (San Sebastian et al., 2007) and PET studies revealed a larger striatal (18)F-DOPA uptake in the CBCA-grafted striatum compared to that receiving Tyrode. No differences were found in the number of surviving dopaminergic cells when comparing both subtantia nigra of UL-grafted animals. However, both UL- and BL-grafted animals showed a bilaterally increased number of TH-GDNF immunoreactive nigral neurons compared to intact and MPTP-untreated monkeys, indicating that in addition to the proven long-term motor benefit, CBCA autograft might exert a neuroprotective effect on the surviving dopaminergic cells.

• Authors: M R Luquin, M Manrique, J Guillén, J Arbizu, C Ordoñez, I Marcilla
• Journal: Brain research (Brain Res) Vol. 1375 Pg. 120-7 (Feb 23 2011) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 21168394 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Glial Cell Line-Derived Neurotrophic Factor
• Radiopharmaceuticals
• fluorodopa F 18
• Dihydroxyphenylalanine
• Tyrosine 3-Monooxygenase
• Dopamine

Topics

• Animals
• Carotid Body (cytology)
• Cell Count
• Cell Transplantation
• Dihydroxyphenylalanine (analogs & derivatives)
• Dopamine (physiology)
• Glial Cell Line-Derived Neurotrophic Factor (biosynthesis)
• Graft Survival
• Immunohistochemistry
• Macaca fascicularis
• Male
• Neurons (transplantation, ultrastructure)
• Phenotype
• Positron-Emission Tomography
• Radiopharmaceuticals
• Substantia Nigra (cytology, diagnostic imaging)
• Tyrosine 3-Monooxygenase (metabolism)