Wallenberg Neuroscience Center, Lund.
J Parkinsons Dis. 2011;1(1):83-92. doi: 10.3233/JPD-2011-11004.
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.
我们证明，在帕金森病（PD）患者的大脑中，移植的人胎脑内神经元可以存活 22 年并延伸轴突。然而，在该患者中，移植物的整体存活率和纤维生长相对较差，这与缺乏明显的临床移植物诱导益处一致。我们比较了 22 年移植物中的神经元形态与另外两个年轻移植物（16 岁和 12 岁）中的神经元形态，这两个移植物依次植入另一名 PD 患者体内。在 22 岁的移植患者中，高达 38%的移植多巴胺能（含色素颗粒）神经元不表达酪氨酸羟化酶和多巴胺转运体，其胞体呈现萎缩。在 12-16 岁的移植物中，不表达这些标志物的色素神经元比例较低。此外，在 22 岁的移植物中，49%的色素神经元在细胞体中显示α-突触核蛋白免疫反应性，其中 1.2%含有路易体。总之，我们的结果表明，移植的多巴胺能神经元可以存活超过 20 年。然而，随着时间的推移，越来越多的移植神经元出现退化迹象。
