Kempermann Gerd, Gast Daniela, Kronenberg Golo, Yamaguchi Masahiro, Gage Fred H
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
Development. 2003 Jan;130(2):391-9. doi: 10.1242/dev.00203.
New neurons are continually generated in the adult hippocampus, but the important question, whether adult neurogenesis is transient or leads to the lasting presence of new neurons, has not yet been answered. Dividing cells were labeled with bromodeoxyuridine (BrdU) and were investigated by means of immunofluorescence and confocal microscopy at several time-points 1 day to 11 months thereafter. BrdU-labeled neurons remained stable in number and in their relative position in the granule cell layer over at least 11 months. This finding implies that the addition of new neurons is not transient and that their final number and localization are determined early. By contrast, expression of immature markers beta-III-tubulin and doublecortin in BrdU-labeled cells, peaked early after division and was not detectable after 4 weeks. In transgenic mice expressing enhanced green fluorescent protein under the nestin promoter none of the BrdU/nestin-positive cells early after division expressed the mature marker NeuN, confirming that no dividing neurons were detected. These new data suggest that new neurons are recruited early from the pool of proliferating progenitor cells and lead to a lasting effect of adult neurogenesis.
成体海马中持续产生新的神经元，但一个重要问题，即成体神经发生是短暂的还是会导致新神经元的持久存在，尚未得到解答。用溴脱氧尿苷（BrdU）标记分裂细胞，并在之后1天至11个月的几个时间点通过免疫荧光和共聚焦显微镜进行研究。BrdU标记的神经元数量及其在颗粒细胞层中的相对位置至少在11个月内保持稳定。这一发现表明新神经元的添加不是短暂的，并且它们的最终数量和定位在早期就已确定。相比之下，BrdU标记细胞中未成熟标记物β-III-微管蛋白和双皮质素的表达在分裂后早期达到峰值，4周后无法检测到。在巢蛋白启动子控制下表达增强型绿色荧光蛋白的转基因小鼠中，分裂后早期没有BrdU/巢蛋白阳性细胞表达成熟标记物NeuN，证实未检测到正在分裂的神经元。这些新数据表明，新神经元早期从增殖祖细胞池中招募，并导致成体神经发生的持久效应。
