Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells

Tetsuro Shingo, S. Todd Sorokan, Takuya Shimazaki, Samuel Weiss

Research output: Contribution to journalArticle

553 Citations (Scopus)

Abstract

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 antiEPO 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.

Original languageEnglish
Pages (from-to)9733-9743
Number of pages11
JournalJournal of Neuroscience
Volume21
Issue number24
Publication statusPublished - 2001 Dec 15
Externally publishedYes

Fingerprint

Neural Stem Cells
Prosencephalon
Erythropoietin
Lateral Ventricles
Neurogenesis
Olfactory Bulb
Neurons
Erythropoietin Receptors
In Vitro Techniques
Interneurons
Neutralizing Antibodies
Stem Cells
Cytokines
Gene Expression
Hypoxia
Antibodies
Brain

Keywords

  • Differentiation
  • Erythropoletin
  • Mash1
  • Neural stem cells
  • Neurogenesis
  • Neuronal progenitors
  • NF-κB

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells. / Shingo, Tetsuro; Todd Sorokan, S.; Shimazaki, Takuya; Weiss, Samuel.

In: Journal of Neuroscience, Vol. 21, No. 24, 15.12.2001, p. 9733-9743.

Research output: Contribution to journalArticle

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