Differential regulation of gliogenesis in the context of adult hippocampal neurogenesis in mice

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Abstract
In adult hippocampal neurogenesis, new neurons appear to originate from a cell with astrocytic properties expressing glial fibrillary acidic protein (GFAP). Also, new astrocytes are generated in the adult dentate gyrus. Whereas the putative astrocyte‐like progenitor cells are consistently S‐100β‐negative, many new astrocytes are S‐100β‐positive. Thus, it is unclear whether the GFAP‐positive progenitor cells are astrocytes in a general sense or rather neural progenitor cells with certain astrocytic characteristics. We therefore investigated the development of GFAP‐expressing cells in the context of adult hippocampal neurogenesis. Proliferating cells could be either GFAP‐positive or doublecortin‐positive (DCX), but never both, indicating two independent populations of dividing cells in the glial and neuronal lineages. Two distinct populations of cells with astroglial properties were detected—one expressing GFAP, the other co‐expressing GFAP and S‐100β. We never found S‐100β‐cells to be in S‐phase. No overlap between neuronal and glial markers was seen at any time point. Thus, astrogenesis occurred in parallel and to some degree independent of adult neurogenesis. The uninterrupted GFAP expression in this lineage, and neuronal markers in the other lineage, argue against a late common precursor for neurogenesis and gliogenesis in the adult hippocampus. Very few newly generated microglia and no new oligodendrocytes were detected. Environmental enrichment and voluntary wheel running—two experimental paradigms with robust stimulatory effects on adult hippocampal neurogenesis—affected hippocampal astrogenesis differentially: Running, but not enrichment, strongly induced net astrogenesis (GFAP/S‐100β), but also GFAP‐positive S‐100β‐negative cells, which thus appear to be a transiently amplifiable intermediate population within the glial lineage.