Enhanced GDNF expression in dopaminergic cells of monkeys grafted with carotid body cell aggregates
2011
Luquin, M.R. | Manrique, M. | Guillén, J. | Arbizu, J. | Ordoñez, C. | Marcilla, I.
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 (¹⁸F-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 ¹⁸F-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.
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