Testosterone and dihydrotestosterone, but not estradiol, enhance survival of new hippocampal neurons in adult male rats
Testosterone and dihydrotestosterone, but not estradiol, enhance survival of new hippocampal neurons in adult male rats
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DOI：
10.1002/dneu.20457
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发表时间：
2007-09-01
影响因子：
3
通讯作者：
Galea, Liisa A. M.
中科院分区：
文献类型：
--
作者：
Spritzer, Mark D.;Galea, Liisa A. M.
过去的研究表明雄激素可能在齿状回内调节成人神经发生中起作用。我们通过控制雄性大鼠的雄激素水平来验证这一假设。给去势或假去势的雄性大鼠注射5-溴2'脱氧尿苷（BrdU）。用免疫组织化学方法对齿状突起中brdu标记的细胞进行可视化和表型分析（神经或胶质）。去势雄鼠齿状回内30天细胞存活率显著降低，但细胞增殖与对照雄鼠相比无显著变化，说明雄激素对细胞存活有积极影响，但对细胞增殖无积极影响。为了研究睾酮对海马细胞存活的作用，从注射BrdU后的第一天开始，雄性小鼠注射睾酮sc，持续30天。较高剂量（0.5和1.0 mg/kg）而不是较低剂量（0.25 mg/kg）的睾酮导致相对于对照组的神经发生显著增加。接下来，我们测试了睾酮的两种主要代谢物，双氢睾酮（DHT）和雌二醇在神经发生中的作用。注射DHT（0.25和0.50 mg/kg）而不注射雌二醇（0.010和0.020 mg/kg） 30天后，海马神经发生显著增加。这些结果表明，睾酮通过雄激素依赖机制通过增加齿状回细胞存活率来促进海马神经发生。(C) 2007 Wiley期刊公司
Past research suggested that androgens may play a role in the regulation of adult neurogenesis within the dentate gyrus. We tested this hypothesis by manipulating androgen levels in male rats. Castrated or sham castrated male rats were injected with 5-Bromo2'deoxyuridine (BrdU). BrdU-labeled cells in the dentate gryus were visualized and phenotyped (neural or glial) using immunohistochemistry. Castrated males showed a significant decrease in 30-day cell survival within the dentate gyrus but there was no significant change in cell proliferation relative to control males, indicating that androgens positively affect cell survival, but not cell proliferation. To examine the role of testosterone on hippocampal cell survival, males were injected with testosterone s.c. for 30 days starting the day after BrdU injection. Higher doses (0.5 and 1.0 mg/ kg) but not a lower dose (0.25 mg/kg) of testosterone resulted in a significant increase in neurogenesis relative to controls. We next tested the role of testosterone's two major metabolites, dihydrotestosterone (DHT), and estradiol, upon neurogenesis. Thirty days of injections of DHT (0.25 and 0.50 mg/kg) but not estradiol (0.010 and 0.020 mg/kg) resulted in a significant increase in hippocampal neurogenesis. These results suggest that testosterone enhances hippocampal neurogenesis via increased cell survival in the dentate gyrus through an androgen-dependent mechanism. (C) 2007 Wiley Periodicals, Inc.