Regulation of nestin expression after cortical ablation in adult rat brain

Regulation of nestin expression after cortical ablation in adult rat brain
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DOI:
10.1016/j.brainres.2003.08.070
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发表时间:
2004-05-22
期刊:
影响因子:
2.9
通讯作者:
Hakim, AM
Hakim, AM
中科院分区:
医学3区
文献类型:
--
作者:
Douen, AG;Dong, L;Hakim, AM

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在胚胎发生过程中,增殖的神经上皮干细胞中巢蛋白的短暂表达是祖细胞分化的信号。尽管成年哺乳动物的大脑中含有很少的巢蛋白,但脑损伤后巢蛋白的显著上调已被报道,这导致了巢蛋白可能参与脑修复的推测。在这项研究中,我们评估了感觉桶皮质消融损伤后巢蛋白表达的时间谱,并研究了对侧须刺激对巢蛋白表达的影响。由于成年哺乳动物的大脑中含有增殖的神经元祖细胞,这些细胞可以被溴脱氧尿苷(BrdU)标记,因此我们也确定了巢蛋白再表达与BrdU标记细胞的关系。Nestin在消融后3天主要在同侧皮质中重新表达。皮层下区巢蛋白未见明显上调。Nestin再表达在病变周围最为明显,但也扩展到整个外侧皮质。损伤后第7天,同侧皮质的巢蛋白表达减少,但损伤后28天,病灶周围的巢蛋白表达仍然明显。Western blot分析消融后3天nestin的表达,证实nestin表达显著增加2倍(p < 0.05)。双免疫荧光标记显示巢蛋白主要表达于星形胶质细胞。我们无法检测到任何与神经元制造者的共定位。然而,brdu标记的细胞,在损伤前很容易在室下区检测到,在消融后3天很容易在病灶周围区域检测到,并伴有巢蛋白在该区域。共聚焦显微镜检测到多个表达巢蛋白的brdu阳性细胞。综上所述,这些数据支持巢蛋白再表达在大脑修复中的潜在作用。(C) 2004 Elsevier B.V.版权所有
During embryogenesis, transient expression of nestin in proliferating neuroepithelial stem cells signals the commitment of progenitor cells to differentiate. Although adult mammalian brain contains very little nestin, significant upregulation of nestin has been reported following cerebral injury, leading to speculation that nestin may be involved in brain repair. In this study, we assessed the temporal profile of nestin expression following ablation injury of the sensory barrel cortex and investigated the influence of contralateral whisker stimulation on nestin expression. Since the adult mammalian brain contains proliferating neuronal progenitor cells that can be labeled with bromodeoxyuridine (BrdU), we also determined the association of nestin reexpression with BrdU-labeled cells. Nestin reexpression was detected predominantly in the ipsilateral cortex 3 days post-ablation. There was no significant nestin upregulation in the subcortical region. Nestin reexpression was most marked surrounding the lesion, but also extended throughout the entire lateral cortex. Nestin in the ipsilateral cortex subsided by day 7, although perilesional nestin expression was still apparent 28 days post-injury. Western blot analysis of nestin expression 3 days post-ablation confirmed a significant two-fold increase in nestin expression (p < 0.05). Double immunofluorescence labeling demonstrated that the majority of nestin expression occurred in astrocytes. We were unable to detect any colocalization with neuronal makers. However, BrdU-labeled cells, which were readily detected in the subventricular zone prior to injury, were readily detected in the perilesional area 3 days postablation, concomitant with nestin in this area. Confocal microscopy detected several BrdU-positive cells expressing nestin. Taken together, the data support a potential role for nestin reexpression in brain repair. (C) 2004 Elsevier B.V. All rights reserved.