Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat
Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat
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DOI：
10.1523/jneurosci.19-14-05792.1999
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发表时间：
1999-07-15
影响因子：
5.3
通讯作者：
Gould, E
中科院分区：
文献类型：
--
作者：
Tanapat, P;Hastings, NB;Gould, E
为了确定是否存在性别差异，在成年期的海马细胞的生产，我们研究了增殖细胞及其后代在成年大鼠使用胸苷类似物溴脱氧尿苷（BrdU）结合免疫组织化学标记的神经元和胶质细胞。此外，为了确定卵巢激素是否影响细胞增殖，我们检测了不同动情周期阶段和卵巢类固醇操作后BrdU标记细胞的数量。BrdU标记的细胞的数量的体视学分析显示，女性产生更多的细胞比男性在齿状回，但不是在脑室下区;新的海马细胞在女性的生产似乎受到卵巢激素水平的影响;卵巢切除术减少了BrdU标记的细胞的数量，雌激素替代逆转的效果。还注意到细胞增殖的自然波动;与发情期和间情期相比，雌性动物在发情前期（雌激素水平最高时）产生更多的细胞。许多这些细胞获得神经元的特性，包括树突的形成和分裂后的翻转64 kDa的表达，不成熟的颗粒神经元的标志物，和钙结合蛋白，成熟的颗粒神经元的标志物。然而，检查固缩细胞的数量和BrdU标记细胞的数量在较长的生存时间显示，许多新的细胞在齿状回最终退化。一致的是，在末次BrdU注射后2周，雌性动物中标记细胞的数量不再高于雄性动物中观察到的数量。这些研究结果表明，雌激素增强的细胞增殖在发情前期的结果在更多的未成熟的神经元在海马结构的女性相比，男性和目前的可能性，这些新的细胞对海马功能产生重要影响。
To determine whether a sex difference exists in the production of hippocampal cells during adulthood, we examined proliferating cells and their progeny in adult rats using the thymidine analog bromodeoxyuridine (BrdU) combined with immunohistochemistry for markers of neurons and glia. Additionally, to determine whether ovarian hormones affect cell proliferation, we examined the numbers of BrdU-labeled cells at different estrous cycle stages and after ovarian steroid manipulation. Stereological analyses of the numbers of BrdU-labeled cells revealed that females produced more cells than males in the dentate gyrus but not in the subventricular zone;The production of new hippocampal cells in females appears to be affected by ovarian hormone levels; ovariectomy diminished the number of BrdU-labeled cells, an effect reversed by estrogen replacement. A natural fluctuation in cell proliferation was also noted; females produced more cells during proestrus (when estrogen levels are highest) compared with estrus and diestrus. Many these cells acquired neuronal characteristics, including the formation of dendrites and expression of Turned-On-After-Division 64 kDa, a marker of immature granule neurons, and the calcium-binding protein calbindin, a marker of mature granule neurons. However, examination of the numbers of pyknotic cells and the numbers of BrdU-labeled cells at longer survival times revealed that many new cells in the dentate gyrus eventually degenerate. Consistently the number of labeled cells in females is no longer higher than that observed in males by 2 weeks after the last BrdU injection. These findings suggest that estrogen-enhanced cell proliferation during proestrus results in more immature neurons in the hippocampal formation of females compared with males and present the possibility that these new cells exert an important influence on hippocampal function.