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The Journal of Neuroscience, January 25, 2006, 26(4):1269-1274; doi:10.1523/JNEUROSCI.4480-05.2006

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

Peter T. Tsai,^1,4 * John J. Ohab,^2 * Nathalie Kertesz,¹ Matthias Groszer,¹ Cheryl Matter,^1,3 Jing Gao,¹ Xin Liu,^1,3,4 Hong Wu,^1,4 and S. Thomas Carmichael²

¹Departments of Molecular and Medical Pharmacology, ²Neurology, and ³Pathology and Laboratory Medicine, and ⁴Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California 90095

Correspondence should be addressed to either of the following: Dr. Hong Wu, Department of Molecular and Medical Pharmacology, Geffen School of Medicine at University of California at Los Angeles, CHS 23-214, Los Angeles, CA 90095, Email: hwu{at}mednet.ucla.edu; or Dr. S. Thomas Carmichael, Department of Neurology, 635 Charles Young Drive South, University of California at Los Angeles, Los Angeles, CA 90095, scarmichael{at}mednet.ucla.edu

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.

Key words: erythropoietin; erythropoietin receptor; neurogenesis; ischemia; post-injury recovery; subventricular zone

---

Received June 23, 2005; revised Dec. 9, 2005; accepted Dec. 14, 2005.

Correspondence should be addressed to either of the following: Dr. Hong Wu, Department of Molecular and Medical Pharmacology, Geffen School of Medicine at University of California at Los Angeles, CHS 23-214, Los Angeles, CA 90095, Email: hwu{at}mednet.ucla.edu; or Dr. S. Thomas Carmichael, Department of Neurology, 635 Charles Young Drive South, University of California at Los Angeles, Los Angeles, CA 90095, scarmichael{at}mednet.ucla.edu

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