Tonchev Anton B, Yamashima Tetsumori
Department of Restorative Neurosurgery, Division of Neuroscience, Kanazawa University Graduate School of Medical Science, Takara-machi 13-1, 920-8641 Kanazawa, Japan.
Exp Neurol. 2006 Mar;198(1):101-13. doi: 10.1016/j.expneurol.2005.11.022. Epub 2006 Jan 19.
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 CA1 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.
成年哺乳动物海马体含有在正常条件下能够产生神经元的神经祖细胞。诸如缺血等脑损伤会导致其在啮齿动物模型中上调，从而在齿状回（DG）和CA1区产生神经发生。成年灵长类动物的DG在正常条件下也具有神经发生潜力，我们之前已经表明，短暂性全脑缺血会增加猴子DG中祖细胞的增殖，在缺血后第二周达到峰值。然而，到目前为止，缺血对灵长类动物海马体中成年生成细胞的长期影响尚未见报道。我们在此表明，在猴子DG中，近15%的成年生成细胞在损伤后至少79天内在齿状颗粒层表达神经元特征。与此同时，DG中的大多数成年新生细胞在颗粒下区保持其定位，具有未成熟祖细胞表型。与DG相反，在缺血后的海马体本身，特别是在CA1区，未观察到神经元产生的迹象，在该区域新生细胞始终为胶质细胞表型。DG中增殖的祖细胞而非与CA1相邻的脑室下区的祖细胞表达神经前体转录因子Emx2、Pax6和Ngn2。综上所述，这些结果表明，成年猴子全脑缺血后海马体中的神经元产生仅限于DG，而在海马体本身并不发生。目前的数据表明，蛋白质Emx2、Pax6和Ngn2是控制成年灵长类动物海马体祖细胞命运的假定分子信号。
