Kempermann G, Kuhn H G, Gage F H
The Salk Institute for Biological Studies, Laboratory of Genetics, La Jolla, California 92037, USA.
J Neurosci. 1998 May 1;18(9):3206-12. doi: 10.1523/JNEUROSCI.18-09-03206.1998.
We demonstrate here that under physiological conditions neurogenesis continues to occur in the dentate gyrus of senescent mice and can be stimulated by living in an enriched environment. Neurogenesis was investigated by confocal microscopy of three-channel immunofluorescent staining for the proliferation marker bromodeoxyuridine (BrdU) and neuronal and glial markers. Quantification was performed with unbiased stereological counting techniques. Neurogenesis decreased with increasing age. Stimulation of adult and aged mice by switching from standard housing to an enriched environment with opportunities for social interaction, exploration, and physical activity for 68 d resulted in an increased survival of labeled cells. Phenotypic analysis revealed that, in enriched living animals, relatively more cells differentiated into neurons, resulting in a threefold net increase of BrdU-labeled neurons in 20-month-old mice (105 vs 32 cells) and a more than twofold increase in 8-month-old mice (684 vs 285 cells) compared with littermates living under standard laboratory conditions. Corresponding absolute numbers of BrdU-positive astrocytes and BrdU-positive cells that did not show colabeling for neuronal or glial markers were not influenced. The effect on the relative distribution of phenotypes can be interpreted as a survival-promoting effect that is selective for neurons. Proliferation of progenitor cells appeared unaffected by environmental stimulation.
我们在此证明，在生理条件下，衰老小鼠齿状回中仍会持续发生神经发生，且生活在丰富环境中可刺激神经发生。通过对增殖标记物溴脱氧尿苷（BrdU）以及神经元和神经胶质标记物进行三通道免疫荧光染色的共聚焦显微镜检查来研究神经发生。使用无偏倚的立体计数技术进行定量分析。神经发生随年龄增长而减少。将成年和老年小鼠从标准饲养环境转换到具有社交互动、探索和身体活动机会的丰富环境中饲养68天，可使标记细胞的存活率增加。表型分析显示，在生活于丰富环境中的动物中，相对更多的细胞分化为神经元，与生活在标准实验室条件下的同窝小鼠相比，20月龄小鼠中BrdU标记的神经元净增加了两倍（105个对32个细胞），8月龄小鼠中增加了两倍多（684个对285个细胞）。BrdU阳性星形胶质细胞以及未显示神经元或神经胶质标记物共标记的BrdU阳性细胞的相应绝对数量未受影响。对表型相对分布的影响可解释为对神经元具有选择性的促存活作用。祖细胞的增殖似乎不受环境刺激的影响。
