A Critical Role of Erythropoietin Receptor in Neurogenesis and Post-Stroke Recovery

Erythropoietin (EPO) is the principal growth factor regulating the production of red blood cells. Recent studies demonstrated that exogenous EPO acts as a neuroprotectant and regulates neurogenesis. Using a genetic approach, we evaluate the roles of endogenous EPO and its classical receptor (EPOR) i...

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Bibliographic Details
Published in:The Journal of neuroscience 2006-01, Vol.26 (4), p.1269-1274
Main Authors: Tsai, Peter T, Ohab, John J, Kertesz, Nathalie, Groszer, Matthias, Matter, Cheryl, Gao, Jing, Liu, Xin, Wu, Hong, Carmichael, S. Thomas
Format: Article
Language:English
Subjects:
Animals
Brain - embryology
Brain - physiopathology
Brief Communications
Cell Division
Cell Lineage
DNA Replication
Erythropoietin - biosynthesis
Erythropoietin - genetics
Erythropoietin - physiology
Gene Expression Regulation, Developmental
In Situ Hybridization
Infarction, Middle Cerebral Artery - pathology
Infarction, Middle Cerebral Artery - physiopathology
Integrases
Mesoderm - cytology
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins - physiology
Neural Crest - cytology
Neural Tube Defects - genetics
Neuroepithelial Cells - metabolism
Neurons - cytology
Receptors, Erythropoietin - biosynthesis
Receptors, Erythropoietin - genetics
Receptors, Erythropoietin - physiology
Regeneration - physiology
Stem Cells - cytology
Viral Proteins
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Summary:Erythropoietin (EPO) is the principal growth factor regulating the production of red blood cells. Recent studies demonstrated that exogenous EPO acts as a neuroprotectant and regulates neurogenesis. Using a genetic approach, we evaluate the roles of endogenous EPO and its classical receptor (EPOR) in mammalian neurogenesis. We demonstrate severe and identical embryonic neurogenesis defects in animals null for either the Epo or EpoR gene, suggesting that the classical EPOR is essential for EPO action during embryonic neurogenesis. Furthermore, by generating conditional EpoR knock-down animals, we demonstrate that brain-specific deletion of EpoR leads to significantly reduced cell proliferation in the subventricular zone and impaired post-stroke neurogenesis. EpoR conditional knockdown leads to a specific deficit in post-stroke neurogenesis through impaired migration of neuroblasts to the peri-infarct cortex. Our results suggest that both EPO and EPOR are essential for early embryonic neural development and that the classical EPOR is important for adult neurogenesis and for migration of regenerating neurons during post-injury recovery.
ISSN:0270-6474
1529-2401
1529-2401
DOI:10.1523/JNEUROSCI.4480-05.2006