Differential neurogenic potential of progenitor cells in dentate gyrus and CA1 sector of the postischemic adult monkey hippocampus
Differential neurogenic potential of progenitor cells in dentate gyrus and CA1 sector of the postischemic adult monkey hippocampus
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DOI：
10.1016/j.expneurol.2005.11.022
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发表时间：
2006-03-01
影响因子：
5.3
通讯作者：
Yamashima, T
中科院分区：
文献类型：
--
作者：
Tonchev, AB;Yamashima, T
成年哺乳动物的海马体含有神经前体细胞，能够在正常条件下产生神经元。脑缺血等脑损伤导致其在啮齿动物模型中表达上调，导致齿状回(DG)和CA区神经发生。成年灵长类动物DG在正常条件下也具有神经发生潜能，我们先前已经证明，短暂性全脑缺血增加了猴DG的祖细胞增殖，在缺血后第二周达到高峰。然而，到目前为止，脑缺血对灵长类动物海马区成年细胞的长期影响还没有被描述。我们在这里显示，近15%的成年产生的细胞在猴子DG中至少79天后在齿状颗粒层表达神经元特征。同时，DG中大多数成体出生的细胞持续定位于颗粒下带，具有未成熟的祖细胞表型。与DG相反，在缺血后的海马区，尤其是CA1区，没有观察到神经元产生的迹象，在那里新生的细胞一直是神经胶质表型。DG的增殖祖细胞表达前神经转录因子Emx2，而与CA1相邻的脑室下区不表达。Pax6和-Ngn2。综上所述，这些结果表明，成年猴全脑缺血后海马区神经元的产生仅限于DG，而不存在于海马区。目前的数据表明Emx2、Pax6和Ngn2蛋白可能是控制成年灵长类海马祖细胞命运的分子信号。(C)2005 Elsevier Inc.保留所有权利。
The adult mammalian hippocampus contains neural progenitor cells capable of neuronal production under normal conditions. Cerebral injuries such as ischemia lead to their upregulation in rodent models, resulting in neurogenesis in the dentate gyrus (DG) and CA sector. The adult primate DG also has neurogenic potential under normal conditions, and we have previously shown that transient global cerebral ischemia increases progenitor cell proliferation in monkey DG, with a peak in the second postischemic week. Until now, however, long-term effects of ischemia on adult-generated cells in the primate hippocampus have not been described. We show here that nearly 15% of the adult-generated cells in monkey DG express neuronal features in the dentate granule layer for at least 79 days after the insult. At the same time, most adult-born cells in DG sustained their localization in the subgranular zone with an immature progenitor phenotype. In contrast to DG, no signs of neuronal production were observed in the postischemic hippocampus proper and in particular in the CA1 sector, where the newly-born cells were consistently of glial phenotype. Proliferating progenitors in DG but not in the subventricular zone adjacent to CA1 expressed the pro-neural transcription factors Emx2. Pax6 and -Ngn2. Taken together, these results suggest that the neuronal production in adult monkey hippocampus after global brain ischemia is limited to DG and does not Occur in the hippocampus proper. The present data implicate the proteins Emx2, Pax6 and Ngn2 as putative molecular signals controlling the fate of progenitor cells of the adult primate hippocampus. (c) 2005 Elsevier Inc. All rights reserved.