Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli
Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli
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DOI：
10.1002/cne.10945
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发表时间：
2003-12-22
影响因子：
2.5
通讯作者：
Kempermann, G
中科院分区：
文献类型：
--
作者：
Kronenberg, G;Reuter, K;Kempermann, G
为了研究成年海马神经发生如何可能起源于干细胞或祖细胞在体内的增殖，我们使用了转基因小鼠表达绿色荧光蛋白（GFP）下的巢蛋白启动子，以确定这些细胞。在描述了具有低增殖活性、特征性形态、血管末端足和被动电生理特性的星形胶质细胞样1型细胞后，我们在这里集中于大量表达nestin-GFP的2型细胞，其缺乏所有这些特征。2型细胞高度增殖，并显示出暗示其参与神经元谱系的迹象。它们可以通过早期神经元标记物doublecortin的共表达的不存在（2a型）或存在（2b型）来细分。第三种类型的增殖细胞是doublecortin阳性，但nestin-GFP阴性（3型）。我们认为，2a，2b和3型细胞反映了早期神经元发育过程中的标志物进展。早期颗粒细胞特异性标志物Prox-1的共表达增加支持了这一观点。1型细胞的低增殖活性随着时间的推移或在“神经性干预”下几乎没有变化，例如环境复杂性（ENR）或自愿体力活动（RUN）的挑战。然而，RUN导致用增殖标记物溴脱氧尿苷（BrdU）标记的2型细胞显著增加。ENR没有引起细胞增殖增加或BrdU标记的2型细胞数量增加，但ENR和RUN都导致更多新生成的细胞缺乏巢蛋白-GFP免疫反应性并表达Prox-1。这些发现使我们能够将早期实验中广泛认为的“增殖”分解为几种细胞类型的相对贡献，代表了神经元发育的最早阶段。(C)2003 Wiley-Liss，Inc.
To study how adult hippocampal neurogenesis might originate from the proliferation of stem or progenitor cells in vivo, we have used transgenic mice expressing green fluorescent protein (GFP) under the nestin promoter to identify these cells. Having described an astrocyte-like type 1 cell with low proliferative activity, a characteristic morphology, vascular end feet, and passive electrophysiological properties, we focused here on the large population of nestin-GFP-expressing type 2 cells, which lack all these features. Type 2 cells were highly proliferative and showed signs suggestive of their involvement in the neuronal lineage. They could be subclassified by the absence (type 2a) or presence (type 2b) of a coexpression of the early neuronal marker doublecortin. A third type of proliferating cells was doublecortin positive but nestin-GFP negative (type 3). We believe that type 2a, 2b, and 3 cells mirror a marker progression during earliest neuronal development. This view is supported by the increasing coexpression of the early granule cell-specific marker Prox-1. The low proliferative activity of type 1 cells showed little change over time or under "neurogenic interventions," such as a challenge by environmental complexity (ENR) or voluntary physical activity (RUN). However, RUN led to a significant increase of type 2 cells labeled with the proliferation marker bromodeoxyuridine (BrdU). ENR did not cause increased cell proliferation or an increased number of BrdU-Iabeled type 2 cells, but both ENR and RUN resulted in more newly generated cells lacking nestin-GFP immunoreactivity and expressing Prox-1. These findings allow us to break down what was broadly perceived as "proliferation" in earlier experiments into the relative contribution of several cell types, representing the earliest steps of neuronal development. (C) 2003 Wiley-Liss, Inc.