Expression pattern of the transcription factor Olig2 in response to brain injuries:: Implications for neuronal repair
Expression pattern of the transcription factor Olig2 in response to brain injuries:: Implications for neuronal repair
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DOI：
10.1073/pnas.0506535102
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发表时间：
2005-12-13
影响因子：
11.1
通讯作者：
Götz, M
中科院分区：
文献类型：
--
作者：
Buffo, A;Vosko, MR;Götz, M
尽管成年哺乳动物脑的某些区域存在神经干细胞和正在进行的神经发生，但损伤后大多数脑区域的神经元不会被替换。为了阐明导致受损大脑皮层神经发生失败的因素，我们研究了急性脑损伤（如刺伤或局灶性缺血）后以及慢性淀粉样蛋白沉积模型中细胞命运决定因素的表达。虽然没有神经原性因子，如Pax6，Mash 1，Ngn 2，在受伤的实质中检测到，我们观察到一个强烈的上调bHLH转录因子Olig2，而不是Olig1，在急性和慢性损伤。为了研究Olig2在脑损伤中的功能，我们在刺伤后2天将含有Olig2显性阴性形式的逆转录病毒载体注射到损伤的皮层中。拮抗Olig2功能导致大量感染细胞产生未成熟神经元，这在注射对照病毒后未观察到。因此，这些数据意味着Olig2作为对脑损伤反应的细胞中的神经发生的阻遏物，并为唤起内源性神经元修复开辟了创新的前景。
Despite the presence of neural stem cells and ongoing neurogenesis in some regions of the adult mammalian brain, neurons are not replaced in most brain regions after injury. With the aim to unravel factors contributing to the failure of neurogenesis in the injured cerebral cortex, we examined the expression of cell fate determinants after acute brain injuries, such as stab wound or focal ischemia, and in a model of chronic amyloid deposition. Although none of the neurogenic factors, such as Pax6, Mash1, Ngn2, was detected in the injured parenchyma, we observed a strong up-regulation of the bHLH transcription factor Olig2, but not Olig1, upon acute and chronic injury. To examine the function of Olig2 in brain lesion, we injected retroviral vectors containing a dominant negative form of Olig2 into the lesioned cortex 2 days after a stab wound. Antagonizing Olig2 function resulted in a significant number of infected cells generating immature neurons that were not observed after injection of the control virus. These data, therefore, imply Olig2 as a repressor of neurogenesis in cells reacting to brain injury and open innovative perspectives toward evoking endogenous neuronal repair.