Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum
Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum
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DOI：
10.1523/jneurosci.0149-06.2006
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发表时间：
2006-06-14
影响因子：
5.3
通讯作者：
Sawamoto, Kazunobu
中科院分区：
文献类型：
--
作者：
Yamashita, Toru;Ninomiya, Mikiko;Sawamoto, Kazunobu
最近的研究表明，成年哺乳动物的大脑有能力再生一些神经元后，各种侮辱。然而，胰岛素诱导的神经发生的确切机制尚未得到证实。在正常脑中，侧脑室的脑室下区（SVZ）中的GFAP表达细胞包括仅产生嗅球神经元的神经源性细胞群。在这里，我们报告的证据表明，中风后，这些细胞能够产生新的神经元外的嗅球。通过细胞类型特异性病毒感染方法标记的SVZ GFAP表达细胞被发现产生神经母细胞，这些神经母细胞在大脑中动脉闭塞后向受损的纹状体迁移。纹状体中的这些神经母细胞形成类似于正常SVZ中的细长链状细胞聚集体，并且观察到这些链与薄的星形胶质细胞突起和血管密切相关。最后，用Cre-loXP系统对绿色荧光标记细胞进行长期追踪，发现SVZ来源的神经母细胞在纹状体分化为成熟神经元，在其中表达神经元特异性核蛋白，并与邻近的细胞形成突触。这些结果突出了SVZ在中风后神经元再生中的作用及其作为各种神经系统疾病的重要治疗靶点的潜力。
Recent studies have revealed that the adult mammalian brain has the capacity to regenerate some neurons after various insults. However, the precise mechanism of insult-induced neurogenesis has not been demonstrated. In the normal brain, GFAP-expressing cells in the subventricular zone (SVZ) of the lateral ventricles include a neurogenic cell population that gives rise to olfactory bulb neurons only. Herein, we report evidence that, after a stroke, these cells are capable of producing new neurons outside the olfactory bulbs. SVZ GFAP-expressing cells labeled by a cell-type-specific viral infection method were found to generate neuroblasts that migrated toward the injured striatum after middle cerebral artery occlusion. These neuroblasts in the striatum formed elongated chain-like cell aggregates similar to those in the normal SVZ, and these chains were observed to be closely associated with thin astrocytic processes and blood vessels. Finally, long-term tracing of the green fluorescent-labeled cells with a Cre-loxP system revealed that the SVZ-derived neuroblasts differentiated into mature neurons in the striatum, in which they expressed neuronal-specific nuclear protein and formed synapses with neighboring striatal cells. These results highlight the role of the SVZ in neuronal regeneration after a stroke and its potential as an important therapeutic target for various neurological disorders.