Saravia Flavia, Beauquis Juan, Pietranera Luciana, De Nicola Alejandro F
Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, 1428 Buenos Aires, Argentina.
Psychoneuroendocrinology. 2007 Jun;32(5):480-92. doi: 10.1016/j.psyneuen.2007.02.012. Epub 2007 Apr 24.
During aging the hippocampus experiences structural, molecular, and functional alterations. Protection from age-related disorders is provided by several factors, including estrogens. Since aging defects start at middle age, we studied if 17 beta-estradiol (E(2)) protected the hippocampus at this age period. Middle age (10-12 month old) male C57Bl/6 mice were implanted sc with E(2) (15 microg) or cholesterol pellets. Ten days afterwards they received bromodeoxyuridine (BrdU) 4 and 2h before killing to study cell proliferation in the dentate gyrus (DG). A pronounced depletion of BrdU+cells in the DG was found in cholesterol-treated middle age mice, accompanied by astrocytosis, and by neuronal loss in the hilus. Middle age mice receiving E(2) showed increased number of BrdU+cells while the other parameters were remarkably attenuated. When steroid treatment was prolonged for 2 months to study migration of cells in the granular layer of the DG, cell migration was unaffected by E(2). However, E(2)-treated middle age mice presented higher cell density and increased staining for doublecortin, a marker for differentiating neurons. Thus, from the three basic steps of adult neurogenesis (proliferation, migration, and differentiation), E(2) stimulated progenitor proliferation - even after long exposure to E(2) studied by Ki67 immunocytochemistry - and differentiation towards a neuronal lineage. This result, in conjunction with recovery from other aging indicators as increased deposits of the aging pigment lipofuscin in DG cells, loss of hilar neurons and astrocytosis supports a wide range protection of hippocampal function of middle age mice by estrogenic hormones.
在衰老过程中，海马体会经历结构、分子和功能上的改变。包括雌激素在内的多种因素可保护机体免受与年龄相关的疾病影响。由于衰老缺陷始于中年，我们研究了17β-雌二醇（E₂）在这个年龄段是否能保护海马体。将中年（10 - 12月龄）雄性C57Bl/6小鼠皮下植入E₂（15微克）或胆固醇微丸。十天后，在处死前4小时和2小时给它们注射溴脱氧尿苷（BrdU），以研究齿状回（DG）中的细胞增殖情况。在接受胆固醇处理的中年小鼠的DG中发现BrdU⁺细胞明显减少，同时伴有星形细胞增生以及海马门区的神经元丢失。接受E₂的中年小鼠BrdU⁺细胞数量增加，而其他参数则明显减弱。当将类固醇治疗延长2个月以研究DG颗粒层中细胞的迁移时，细胞迁移不受E₂影响。然而，接受E₂治疗的中年小鼠呈现出更高的细胞密度以及双皮质素（一种分化神经元的标志物）染色增加。因此，在成体神经发生的三个基本步骤（增殖、迁移和分化）中，E₂刺激祖细胞增殖——即使在通过Ki67免疫细胞化学研究的长期暴露于E₂之后——并向神经元谱系分化。这一结果，连同从其他衰老指标的恢复情况，如DG细胞中衰老色素脂褐素沉积增加、海马门区神经元丢失和星形细胞增生，支持雌激素对中年小鼠海马体功能具有广泛的保护作用。
