Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
Brain. 2011 Nov;134(Pt 11):3249-63. doi: 10.1093/brain/awr256.
There are many indications that neurogenesis is impaired in Parkinson's disease, which might be due to a lack of dopamine in the subventricular zone. An impairment in neurogenesis may have negative consequences for the development of new therapeutic approaches in Parkinson's disease, as neural stem cells are a potential source for endogenous repair. In this study, we examined the subventricular zone of 10 patients with Parkinson's disease and 10 age- and sex-matched controls for proliferation and neural stem cell numbers. We also included five cases with incidental Lewy body disease, which showed Parkinson's disease pathology but no clinical symptoms and thus did not receive dopaminergic treatment. We quantified the neural stem cell number and proliferative capacity in the subventricular zone of these three donor groups. We found subventricular neural stem cells in each donor, with a high variation in number. We did not observe significant differences in neural stem cell number or in proliferation between the groups. Additionally, we were able to culture neural stem cells from post-mortem brain of several patients with Parkinson's disease, confirming the presence of viable neural stem cells in these brains. We have also examined the subventricular zone of a chronic, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model, and again found no effect of dopaminergic denervation on precursor proliferation. Lastly, we investigated the proliferation capacity of two different human neural stem cell lines in response to dopamine. Both cell lines did not respond with a change in proliferation to treatment with dopamine agonists and an antagonist. In summary, the adult neural stem cell pool in the subventricular zone was not clearly affected in the human parkinsonian brain or a Parkinson's disease mouse model. Furthermore, we did not find evidence that dopamine has a direct effect on human neural stem cell proliferation in vitro. Thus, we conclude that the number of adult neural stem cells is probably not diminished in the parkinsonian brain and that dopamine depletion most likely has no effect on human neural stem cells.
有许多迹象表明，神经发生在帕金森病中受到损害，这可能是由于侧脑室下区缺乏多巴胺。神经发生的损伤可能对帕金森病新的治疗方法的发展产生负面影响，因为神经干细胞是内源性修复的潜在来源。在这项研究中，我们检查了 10 例帕金森病患者和 10 例年龄和性别匹配的对照者的侧脑室下区的增殖和神经干细胞数量。我们还包括 5 例偶然的路易体病，这些病例表现出帕金森病的病理学但没有临床症状，因此没有接受多巴胺治疗。我们量化了这三组供体的侧脑室下区神经干细胞的数量和增殖能力。我们在每个供体中都发现了侧脑室下的神经干细胞，其数量变化很大。我们没有观察到各组之间神经干细胞数量或增殖有显著差异。此外，我们能够从几位帕金森病患者的死后大脑中培养神经干细胞，证实这些大脑中存在有活力的神经干细胞。我们还检查了慢性 1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的帕金森病小鼠模型的侧脑室下区，再次发现多巴胺能神经支配的丧失对前体细胞增殖没有影响。最后，我们研究了两种不同的人神经干细胞系对多巴胺的增殖能力。两种细胞系对多巴胺激动剂和拮抗剂的处理都没有表现出增殖的变化。总之，在帕金森病患者的大脑或帕金森病小鼠模型中，侧脑室下区的成年神经干细胞池没有明显受到影响。此外，我们没有发现多巴胺对体外人神经干细胞增殖有直接影响的证据。因此，我们得出结论，帕金森病大脑中成年神经干细胞的数量可能没有减少，多巴胺耗竭很可能对人神经干细胞没有影响。
