Studies on neurogenesis in the adult human brain

Abstract: Many studies on neurogenesis in adult dentate gyrus (DG) have been performed on rodents and other mammalian species, but only a few on adult human DG.  This study is focusing on neurogenesis in adult human DG. To characterize the birth of cells in DG, the expression of the cell proliferation marker Ki67 was examined using immunohistochemistry. Ki67-positive labelling was indeed observed in the granular cell layer and the molecular layer of dentate gyrus and in the hilus of hippocampus, as well as in the subgranular zone (SGZ). The Ki67 positive nuclei could be divided into three groups, based on their morphology and position, suggesting that one of the groups represents neuronal precursors. Fewer Ki67 positive cells were seen in aged subjects and in subjects with an alcohol abuse. When comparing the Ki67 positive cells and the amount of blood vessels as determined by anti factor VIII, no systematic pattern could be discerned. To identify possible stem/progenitor cells in DG a co-labelling with nestin and glial fibrillary acid protein was carried out. Co-labelling was found in the SGZ, but most of the filaments were positive for just one of the two antibodies. Antibodies to detect immature/mature neurons were also used to investigate adult human neurogenesis in DG. The immature marker βIII-tubulin showed a weak expression. The other two immature markers (PSA-NCAM and DCX) used did not work, probably since they were not cross-reacting against human tissue. In summary, this study shows that new cells are continuously formed in the adult human hippocampus, but at a slower pace compared to the rat, and that some of these new cells may represent neuronal precursors.