Tsai Peter T, Ohab John J, Kertesz Nathalie, Groszer Matthias, Matter Cheryl, Gao Jing, Liu Xin, Wu Hong, Carmichael S Thomas
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095, USA.
J Neurosci. 2006 Jan 25;26(4):1269-74. doi: 10.1523/JNEUROSCI.4480-05.2006.
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.
促红细胞生成素（EPO）是调节红细胞生成的主要生长因子。最近的研究表明，外源性EPO可作为一种神经保护剂并调节神经发生。我们采用遗传学方法评估内源性EPO及其经典受体（EPOR）在哺乳动物神经发生中的作用。我们证明，Epo或EpoR基因缺失的动物存在严重且相同的胚胎神经发生缺陷，这表明经典的EPOR在胚胎神经发生过程中对EPO发挥作用至关重要。此外，通过构建条件性EpoR基因敲低动物，我们证明脑特异性缺失EpoR会导致脑室下区细胞增殖显著减少以及中风后神经发生受损。EpoR条件性敲低通过损害神经母细胞向梗死周围皮质的迁移，导致中风后神经发生出现特定缺陷。我们的研究结果表明，EPO和EPOR对早期胚胎神经发育均至关重要，且经典的EPOR对成体神经发生以及损伤后恢复过程中再生神经元的迁移也很重要。
