Transient expression of doublecortin during adult neurogenesis

Transient expression of doublecortin during adult neurogenesis
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DOI:
10.1002/cne.10874
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发表时间:
2003-12-01
影响因子:
2.5
通讯作者:
Kuhn, HG
Kuhn, HG
中科院分区:
医学3区
文献类型:
--
作者:
Brown, JP;Couillard-Després, S;Kuhn, HG

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在中枢神经系统发育过程中,微管结合蛋白双皮质素(DCX)的表达与神经母细胞的迁移有关。除了这种发育作用外,DCX在成年哺乳动物大脑的某些区域的表达仍然很高。这些区域,主要是齿状回和侧脑室壁以及吻侧迁移流和嗅球,在成年后仍保留产生新神经元的能力。成人神经发生通常是通过将溴脱氧尿苷(BrdU)掺入分裂细胞并将BrdU阳性细胞与成熟神经元标记物进行标记来检测的。为了阐明DCX是否可以作为成人神经发生的替代指标,我们研究了DCX在成人大脑神经发生区域的时间表达模式。对新生细胞的分析表明,DCX在增殖的祖细胞和新生的神经母细胞中短暂表达。当新生成的细胞开始表达成熟的神经元标记物时,DCX的免疫反应性急剧下降到检测水平以下,此后一直无法检测到。DCX在神经源性祖细胞/神经母细胞中的瞬时表达模式表明DCX可以发展成为成人神经发生的合适标记物,并可能提供BrdU标记的替代方法。我们的观察结果进一步支持了这一假设,根据先前报道的衰老齿状回神经发生减少,齿状回中表达dcx的细胞数量随着年龄的增长而减少。(C) 2003 Wiley-Liss, Inc。
During development of the central nervous system, expression of the microtubule binding protein doublecortin (DCX) is associated with migration of neuroblasts. In addition to this developmental role, expression of DCX remains high within certain areas of the adult mammalian brain. These areas, mainly the dentate gyrus and the lateral ventricle wall in conjunction with the rostral migratory stream and olfactory bulb, retain the capacity to generate new neurons into adulthood. Adult neurogenesis is typically detected by incorporation of bromodeoxyuridine (BrdU) into dividing cells and colabeling of BrdU-positive cells with markers for mature neurons. To elucidate whether DCX could act as an alternative indicator for adult neurogenesis, we investigated the temporal expression pattern of DCX in neurogenic regions of the adult brain. Analysis of newly generated cells showed that DCX is transiently expressed in proliferating progenitor cells and newly generated neuroblasts. As the newly generated cells began expressing mature neuronal markers, DCX immunoreactivity decreased sharply below the level of detection and remained undetectable thereafter. The transient expression pattern of DCX in neuronal committed progenitor cells/neuroblasts indicates that DCX could be developed into a suitable marker for adult neurogenesis and may provide an alternative to BrdU labeling. This assumption is further supported by our observation that the number of DCX-expressing cells in the dentate gyrus was decreased with age according to the reduction of neurogenesis in the aging dentate gyrus previously reported. (C) 2003 Wiley-Liss, Inc.