14 September 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.
Reference:Seri B, Garcia-Verdugo JM, McEwen BS, Alvarez-Buylla A. Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci. 2001 Sep 15;21(18):7153-60. Abstract