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Signs of Degeneration in 12–22-Year Old Grafts of Mesencephalic Dopamine Neurons in Patients with Parkinson's Disease

Article type: Research Article

Authors: Kurowska, Zuzanna; | Englund, Elisabet | Widner, Håkan | Lindvall, Olle | Li, Jia-Yi; | Brundin, Patrik

Affiliations: Neuronal Survival Unit, Wallenberg Neuroscience Center, Lund, Sweden | Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Lund, Sweden | Department of Neuropathology, University Hospital, Lund University, Lund, Sweden | Division of Neurology, Department of Clinical Sciences, Lund University, Lund, Sweden | Laboratory of Neurogenesis and Cell Therapy, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden

Note: [] Senior authors.

Note: [] Correspondence to: Dr. Jia-Yi Li, Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Lund University, BMC A10, 221 84 Lund, Sweden. Tel.: +46 46 2220525; Fax: +46 462220531; E-mail: [email protected] Senior authors.

Note: [] Senior authors.

Keywords: Neural, transplantation, graft survival, dopamine, phenotype, tyrosine hydroxylase, alpha-synuclein, Lewy bodies

DOI: 10.3233/JPD-2011-11004

Journal: Journal of Parkinson's Disease, vol. 1, no. 1, pp. 83-92, 2011

Published: 2011
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Abstract

We demonstrate that grafted human fetal mesencephalic neurons can survive and extend axons for 22 years in the brain of a patient with Parkinson's disease (PD). In this patient, the overall survival and fiber outgrowth of the grafts were, however, relatively poor, which is consistent with the lack of significant clinical graft-induced benefit. We have compared the morphology of neurons in the 22-year old grafts with those in two younger grafts (16- and 12-year old), which were sequentially implanted in another PD patient. In the case with the 22-year-old transplant, a high proportion (up to 38%) of the grafted dopaminergic (pigment-granule containing) neurons do not express tyrosine hydroxylase and dopamine transporter and their perikarya appear atrophic. The proportion of pigmented neurons not expressing these markers is lower in the 12–16 year old grafts. Furthermore, in the 22-year-old graft, 49% of the pigmented neurons display α-synuclein immunoreactivity in the cell body and 1.2% of them contain Lewy bodies. In conclusion, our results show that grafted dopaminergic neurons can survive for more than two decades. However, over time an increasing proportion of grafted neurons exhibit signs of degeneration.

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