RT Journal Article
SR Electronic
T1 Erythropoietin Regulates the <em>In Vitro</em> and <em>In Vivo</em> Production of Neuronal Progenitors by Mammalian Forebrain Neural Stem Cells
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9733
OP 9743
DO 10.1523/JNEUROSCI.21-24-09733.2001
VO 21
IS 24
A1 Tetsuro Shingo
A1 S. Todd Sorokan
A1 Takuya Shimazaki
A1 Samuel Weiss
YR 2001
UL http://www.jneurosci.org/content/21/24/9733.abstract
AB Recent studies have shown that neurogenesis is enhanced after hypoxia and that erythropoietin (EPO), an inducible cytokine, is produced in the brain as part of the intrinsic hypoxia response. Thus, we asked whether EPO might regulate neurogenesis by forebrain neural stem cells (NSCs). We found that EPO receptors are expressed in the embryonic germinal zone during neurogenesis as well as in the adult subventricular zone, which continues to generate neurons throughout adulthood. Cultured NSCs exposed to a modest hypoxia produced two- to threefold more neurons, which was associated with an elevation in EPO gene expression. The enhanced neuron production attributable to hypoxia was mimicked by EPO and blocked by coadministration of an EPO neutralizing antibody. EPO appears to act directly on NSCs, promoting the production of neuronal progenitors at the expense of multipotent progenitors. EPO infusion into the adult lateral ventricles resulted in a decrease in the numbers of NSCs in the subventricular zone, an increase in newly generated cells migrating to the olfactory bulb, and an increase in new olfactory bulb interneurons. Infusion of anti-EPO antibodies had the opposite effect: an increase in the number of NSCs in the subventricular zone and a decrease in the number of newly generated cells migrating to the bulb. These findings suggest that EPO is an autocrine–paracrine factor, capable of regulating the production of neuronal progenitor cells by forebrain NSCs.