14 Sep 2001

Astrocytes are the stem cells that generate new neurons in the mammalian hippocampus, according to a report in the September 15 Journal of Neuroscience. This result appears to match results from the subventricular zone (SVZ) bordering the lateral ventricle, where astrocytes have also been pegged as the stem cells.

In experiments paralleling those used to identify the SVZ stem cells, Bettina Seri and Bruce McEwen of Rockefeller University in New York, with Arturo Alvarez-Buylla of the University of California, San Francisco, and Jose Manuel Garcia-Verdugo of the University of Valencia in Spain, used light and electron microscopy to find actively dividing cells (indicated by the proliferation marker BrdU) in the subgranular layer (SGL) of the mouse hippocampus.

More than half of these cells also had the glial marker GFAP. At the electron-microscopic level, the GFAP-positive cells resembled the astrocytes dubbed "B" cells in the SVZ, leading the researchers to term these "SGL B cells." The BrdU-positive but GFAP-negative cells did not have the morphological characteristics of astrocytes. The authors call these "D" cells and hypothesize that they might be precursors or descendants of the B cells.

In order to investigate which comes first, the researchers "reset" the mitotic process by chemically eliminating all actively dividing cells. Two days after mitosis was interrupted only B cells were present in the SGL. D cells gradually reappeared, returning to control levels after 15 days. This led the researchers to propose that the astrocyte-like B cells give rise to D cells as an intermediate step in neurogenesis.

To show that these astrocytes were in fact the precursors of mature, newly formed neurons, a retrovirus carrying a reporter gene (AP) was targeted at GFAP-positive cells. Thirty days later the researchers found mature, AP-labeled granule neurons in the dentate gyrus of the hippocampus. "These results reveal the origins of new neurons in the adult hippocampus," the authors conclude.—Hakon Heimer