Synaptic dopamine release from embryonic nigral transplants has been monitored in the striatum of a patient with Parkinson's disease using [11C]-raclopride positron emission tomography to measure dopamine D2 receptor occupancy by the endogenous transmitter. In this patient, who had received a transplant in the right putamen 10 years earlier, grafts had restored both basal and drug-induced dopamine release to normal levels. This was associated with sustained, marked clinical benefit and normalized levels of dopamine storage in the grafted putamen. Despite an ongoing disease process, grafted neurons can thus continue for a decade to store and release dopamine and give rise to substantial symptomatic relief.
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Brundin, P., Duan, W.-M. & Sauer, H. in Functional Neural Transplantation (eds. Dunnett, S. B. & Björklund, A.) 9–46 (Raven, New York, 1994).
Annett, L. E. in Functional Neural Transplantation (eds. Dunnett, S. B. & Björklund, A.) 71–102 (Raven, New York, 1994).
Olanow, C. W., Kordower, J. H. & Freeman, T. B. Fetal nigral transplantation as a therapy for Parkinson's disease. Trends Neurosci. 19, 102–109 (1996).
Lindvall, O. Cerebral implantation in movement disorders: State of the art. Mov. Disord. 14, 201–205 (1999).
Kordower, J. H. et al. Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson's disease. N. Engl. J. Med. 332, 1118–1124 (1995).
Kordower, J. H. et al. Fetal nigral grafts survive and mediate clinical benefit in a patient with Parkinson's disease. Mov. Disord. 13, 383–393 (1998).
Carson, R. E. et al. Quantification of amphetamine-induced changes in [11C]Raclopride binding with continuous infusion. J. Cereb. Blood Flow Metab. 17, 437–447 (1997).
Koepp, M. J. et al. Evidence for striatal dopamine release during a videogame. Nature 393, 266–268 (1998).
Lindvall, O. et al. Transplantation of fetal dopamine neurons in Parkinson's disease: 1-year clinical and neurophysiological observations in two patients with putaminal implants. Ann. Neurol. 31, 155–165 (1992).
Lindvall, O. et al. Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson's disease. Ann. Neurol. 35, 172–180 (1994).
Wenning, G. K. et al. Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease. Ann. Neurol. 42, 95–107 (1997).
Seeman, P. et al. Human brain D1 and D2 receptors in schizophrenia, Alzheimer's, Parkinson's and Huntington's diseases. Neuropsychopharmacology 1, 5–15 (1987).
Rinne, U. K. et al. Positron emission tomography demonstrates dopamine D2 receptor supersensitivity in the striatum of patients with early Parkinson's disease. Mov. Disord. 5, 55–59 (1990).
Sawle, G. V., Playford, E. D., Brooks, D. J., Quinn, N. & Frackowiak, R. S. J. Asymmetrical pre-synaptic and post-synaptic changes in the striatal dopamine projection in dopa naive parkinsonism. Brain 116, 853–867 (1993).
Antonini, A. et al. [11C]-raclopride and positron emission tomography in previously untreated patients with Parkinson's disease: influence of L-dopa and lisuride therapy on striatal dopamine D2 receptors. Neurology 44, 1325–1329 (1994).
Elsworth, J. H. et al. Upregulation of striatal D2 receptors in the MPTP-treated vervet monkey is reversed by grafts of fetal ventral mesencephalon: an autoradiographic study. Brain Res. 795, 55–62 (1998).
Laruelle, M. et al. Microdialysis and SPECT measurements of amphetamine-induced release in nonhuman primates. Synapse 25, 1–14 (1997).
Gunn, R. N., Lammertsma, A. A., Hume, S. P. & Cunningham, V. J. Parametric imaging of ligand-receptor binding in PET using a simplified reference region model. Neuroimage 6, 279–287 (1997).
Studholme, C., Derek, L. G. & Hawkes D.J. Automated three-dimensional registration of magnetic resonance and positron emission tomography brain images by multiresolution optimization of voxel similarity measures. Med. Phys. 24, 25–35 (1997).
Brooks, D. J. et al. Differing patterns of striatal 18F-dopa uptake in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. Ann. Neurol. 28, 547–555 (1990).
This study was supported by grants from the Swedish Medical Research Council, the European Union (Biomed 2 grant BMH4-CT95-0341), the UK Parkinson's Disease Society and the Kock, Wiberg, Söderberg and King Gustav V and Queen Victoria Foundations. We also thank J.B., whose participation made this study possible.
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Piccini, P., Brooks, D., Björklund, A. et al. Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient. Nat Neurosci 2, 1137–1140 (1999). https://doi.org/10.1038/16060
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