Possibility for neurogenesis in substantia nigra of parkinsonian brain
Possibility for neurogenesis in substantia nigra of parkinsonian brain
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DOI：
10.1002/ana.20506
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发表时间：
2005-07
影响因子：
11.2
通讯作者：
K. Yoshimi;Yong Ren;T. Seki;M. Yamada;H. Ooizumi;M. Onodera;Yuko Saito;S. Murayama;H. Okano;Y. Mizuno;H. Mochizuki
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文献类型：
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作者：
K. Yoshimi;Yong Ren;T. Seki;M. Yamada;H. Ooizumi;M. Onodera;Yuko Saito;S. Murayama;H. Okano;Y. Mizuno;H. Mochizuki
最近关于抗抑郁药物促进海马神经发生的研究表明，促进神经发生是治疗神经退行性疾病的一种潜在的有效方法。在这项研究中，我们评估了动物和包括帕金森病(PD)患者在内的尸检脑中的黑质神经发生。首先，用逆转录病毒转导绿色荧光蛋白标记黑质中的增殖细胞，这是一种有效的标记神经干细胞的方法。随后进行了标记细胞的分化，在注射后4周，无论是完整的啮齿动物还是用1-甲基-4-苯基-1，2，3，6-四氢吡啶处理的啮齿动物，许多转导细胞都变成了小胶质细胞，但没有分化为酪氨酸羟化酶阳性神经元。其次，在啮齿动物、灵长类动物和人类中脑的黑质中检测到聚唾液酸(PSA)样免疫反应，表明新分化的神经元。部分PD患者黑质网状部可见大量PSA阳性细胞。在大鼠和猕猴中，多巴胺缺乏的大脑半球比完好的一侧显示出更多的PSA染色。少数酪氨酸羟化酶阳性细胞呈PSA阳性。我们的结果提示加强帕金森病的神经重建，这可能在设计抗帕金森病进展的新疗法方面很重要。Ann Neurol 2005
Recent studies of enhanced hippocampal neurogenesis by antidepressants suggest enhancement of neurogenesis is a potentially effective therapy in neurodegenerative diseases. In this study, we evaluated nigral neurogenesis in animals and autopsy brains including patients with Parkinson's disease (PD). First, proliferating cells in substantia nigra were labeled with retroviral transduction of green fluorescent protein, which is an efficient method to label neuronal stem cells. Subsequent differentiation of labeled cells was followed; many transduced cells became microglia, but no differentiation into tyrosine hydroxylase–positive neurons was detected at 4 weeks after injection, in both intact rodents and those treated with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine. Second, polysialic acid (PSA)–like immunoreactivity, indicative of newly differentiated neurons, was detected in the substantia nigra of rodent, primate, and human midbrains. A large number of PSA‐positive cells were detected in the substantia nigra pars reticulata of some patients with PD. In rats and a macaque monkey, the dopamine‐depleted hemispheres showed more PSA staining than the intact side. A small number of tyrosine hydroxylase–positive cells were PSA‐positive. Our results suggest enhanced neural reconstruction in PD, which may be important in the design of new therapies against the progression of PD. Ann Neurol 2005