年龄相关的海马前体细胞亚群和神经发生的影响。

Age-related effects on hippocampal precursor cell subpopulations and neurogenesis.

机构信息

Department of Neurology, University Hospital Jena, Erlanger Allee 101, D-07747 Jena, Germany.

出版信息

Neurobiol Aging. 2011 Oct;32(10):1906-14. doi: 10.1016/j.neurobiolaging.2009.11.011. Epub 2009 Dec 16.

Abstract

Hippocampal neurogenesis continuously declines in the aging brain but only little is known about age-related alterations in the subgranular zone (SGZ) of the dentate gyrus which accommodates different subpopulations of precursor cells. Here, we examined the age-related effects on total number and proliferation rate of distinct precursor cell populations in the dentate gyrus of 3 and 16 months old transgenic pNestin-GFP mice. Following a single injection of bromodeoxyuridine (BrdU) we observed a significant reduction of all proliferating precursor subtypes in aged mice compared to young controls. Stereological analysis further revealed that this decreased proliferation was not only caused by a general reduction in total number of precursor subtypes but also by a subtype-specific alteration of the proliferation rate. Whereas radial glia-like and early neuronal precursor cells demonstrate decreased proliferation rates, no difference was found for doublecortin-positive precursors. Additional long-term experiments further revealed that these age-related alterations in the proliferative zone were accompanied by a strongly decreased neurogenesis while hippocampal function was not impaired.

摘要

海马神经发生在衰老的大脑中持续下降,但对于齿状回颗粒下区(SGZ)中与不同前体细胞亚群相适应的与年龄相关的变化知之甚少。在这里,我们研究了年龄对转基因 pNestin-GFP 小鼠 3 个月和 16 个月大的齿状回中不同前体细胞群体总数和增殖率的影响。在单次注射溴脱氧尿苷(BrdU)后,我们观察到与年轻对照组相比,老年小鼠所有增殖前体细胞亚型的数量都显著减少。体视学分析进一步表明,这种增殖减少不仅是由于前体细胞亚型总数的普遍减少,还与增殖率的特定亚型改变有关。而放射状胶质样和早期神经元前体细胞表现出增殖率降低,双皮质素阳性前体细胞则没有差异。进一步的长期实验还表明,增殖区的这些与年龄相关的变化伴随着神经发生的强烈减少,而海马功能没有受损。

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