title: 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.affiliation: Laboratory of Regenerative Therapy, Centre for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Navarra, Spain. jbustama@psb.uji.es
authors.forename: M R
authors.initials: MR
authors.lastname: Luquin
authors.forename: M
authors.initials: M
authors.lastname: Manrique
authors.forename: J
authors.initials: J
authors.lastname: Guillén
authors.forename: J
authors.initials: J
authors.lastname: Arbizu
authors.forename: C
authors.initials: C
authors.lastname: Ordoñez
authors.forename: I
authors.initials: I
authors.lastname: Marcilla
mesh_terms: D000818:Animals; D002344:Carotid Body / Q000166:cytology*; D002452:Cell Count; D017690:Cell Transplantation; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives; D004298:Dopamine / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis*; D006085:Graft Survival; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008297:Male; D009474:Neurons / Q000637:transplantation* / Q000648:ultrastructure; D010641:Phenotype; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013378:Substantia Nigra / Q000166:cytology / Q000000981:diagnostic imaging; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D019275:Radiopharmaceuticals; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine