The majority of newly generated cells in the adult mouse substantia nigra express low levels of Doublecortin, but their proliferation is unaffected by 6‐OHDA‐induced nigral lesion or Minocycline‐mediated inhibition of neuroinflammation
The majority of newly generated cells in the adult mouse substantia nigra express low levels of Doublecortin, but their proliferation is unaffected by 6‐OHDA‐induced nigral lesion or Minocycline‐mediated inhibition of neuroinflammation
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DOI：
10.1111/ejn.12269
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发表时间：
2013-09
影响因子：
3.4
通讯作者：
M. M. Worlitzer-M.;T. Viel;A. Jacobs;J. Schwamborn
中科院分区：
文献类型：
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作者：
M. M. Worlitzer-M.;T. Viel;A. Jacobs;J. Schwamborn
帕金森病的特征在于黑质（SN）中多巴胺能神经元的选择性损失。然而，再生内源性神经发生是否发生在帕金森病和非帕金森病大脑的哺乳动物SN中仍然存在争议。在这里，我们测试了在生理条件下和6-羟基多巴胺（6-OHDA）帕金森病小鼠模型中，SN中的增殖细胞及其神经发生潜力是否会受到抗炎治疗的影响。我们报告说，大多数新产生的黑质细胞是阳性的双皮质素（Dcx），这是一个经常使用的标记神经祖细胞。然而，Dcx在这些细胞中的表达水平远低于室管膜下区的神经前体细胞和齿状回神经前体细胞。此外，这些新产生的黑质细胞对神经元谱系标记物如TuJ 1和NeuN是阴性的。因此，他们的神经元承诺是值得怀疑的。相反，我们在SN中发现了少突胶质细胞生成和星形胶质细胞增生的证据。最后，米诺环素或6-OHDA诱导的损伤对神经炎症的短期或长期抑制都不会影响我们疾病范例中新生成细胞的数量。我们在SN中成人产生的Dcx+细胞的发现为理解SN的细胞组成和再生能力增加了重要数据。
Parkinson's disease is characterized by a selective loss of dopaminergic neurons in the substantia nigra (SN). However, whether regenerative endogenous neurogenesis is taking place in the mammalian SN of parkinsonian and non‐parkinsonian brains remains of debate. Here, we tested whether proliferating cells in the SN and their neurogenic potential would be affected by anti‐inflammatory treatment under physiological conditions and in the 6‐hydroxy‐dopamine (6‐OHDA) Parkinson's disease mouse model. We report that the majority of newly generated nigral cells are positive for Doublecortin (Dcx), which is an often used marker for neural progenitor cells. Yet, Dcx expression levels in these cells were much lower than in neural progenitor cells of the subventricular zone and the dentate gyrus neural progenitor cells. Furthermore, these newly generated nigral cells are negative for neuronal lineage markers such as TuJ1 and NeuN. Therefore, their neuronal commitment is questionable. Instead, we found evidence for oligodendrogenesis and astrogliosis in the SN. Finally, neither short‐term nor long‐term inhibition of neuroinflammation by Minocycline‐ or 6‐OHDA‐induced lesion affected the numbers of newly generated cells in our disease paradigm. Our findings of adult generated Dcx+ cells in the SN add important data for understanding the cellular composition and consequently the regenerative capacity of the SN.