Ninomiya Mikiko, Yamashita Toru, Araki Nobuo, Okano Hideyuki, Sawamoto Kazunobu
Bridgestone Laboratory of Developmental and Regenerative Neurobiology, Keio University School of Medicine, 35 Shinanomachi, Tokyo 160-8582, Japan.
Neurosci Lett. 2006 Jul 31;403(1-2):63-7. doi: 10.1016/j.neulet.2006.04.039. Epub 2006 May 15.
In the subventricular zone (SVZ) of the adult mammalian brain, neural stem cells continually produce transit-amplifying precursors, which generate neuroblasts migrating into the olfactory bulb. Previous studies have suggested that SVZ cells also have the capacity to generate some striatal neurons after cerebral ischemia. The infusion of epidermal growth factor (EGF) has been demonstrated to increase the number of these regenerated neurons. However, which cell types in the SVZ are stimulated to proliferate or differentiate after EGF infusion remains unknown. In this paper, we demonstrated that cerebral ischemia results in an increase in the number of EGF receptor (EGFR)-positive transit-amplifying cells in the SVZ. EGF infusion into the ischemic brain caused the number of transit-amplifying cells to increase and the number of neuroblasts to decrease. On the other hand, after an interval of 6 days after the discontinuation of EGF infusion, a significant increase in the number of neuroblasts was found, both in the striatum and the SVZ. These results suggest that the replacement of neurons in injured striatum can be enhanced by an EGF-induced expansion of transit-amplifying cells in the SVZ.
在成年哺乳动物大脑的脑室下区(SVZ),神经干细胞持续产生过渡放大前体细胞,这些前体细胞产生迁移至嗅球的神经母细胞。先前的研究表明,脑缺血后SVZ细胞也有能力生成一些纹状体神经元。已证明注入表皮生长因子(EGF)可增加这些再生神经元的数量。然而,注入EGF后SVZ中哪些细胞类型被刺激增殖或分化仍不清楚。在本文中,我们证明脑缺血导致SVZ中表皮生长因子受体(EGFR)阳性的过渡放大细胞数量增加。向缺血脑内注入EGF导致过渡放大细胞数量增加而神经母细胞数量减少。另一方面,在停止注入EGF 6天后,在纹状体和SVZ中均发现神经母细胞数量显著增加。这些结果表明,EGF诱导的SVZ中过渡放大细胞的扩增可增强受损纹状体中神经元的替代。