Differential neurogenic potential of progenitor cells in dentate gyrus and CA1 sector of the postischemic adult monkey hippocampus

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.