Repeated estradiol administration alters different aspects of neurogenesis and cell death in the hippocampus of female, but not male, rats
Repeated estradiol administration alters different aspects of neurogenesis and cell death in the hippocampus of female, but not male, rats
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DOI：
10.1016/j.neuroscience.2007.10.071
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发表时间：
2008-04-09
期刊：
影响因子：
3.3
通讯作者：
Galea, L. A. M.
中科院分区：
文献类型：
--
作者：
Barker, J. M.;Galea, L. A. M.
雌二醇已被证明具有神经保护作用，而急性雌二醇治疗可促进女性大脑中的海马神经发生。然而，关于反复服用雌二醇对女性大脑的影响，以及雌二醇对男性大脑的影响，人们知之甚少。成年雄性和雌性去性腺大鼠注射5-溴-2-脱氧尿苷(BrdU)(200 mg/kg)，24 h后皮下注射苯甲酸雌二醇(33µg/kg)或赋形剂，每日1次，连续15天。在第16天，灌流动物并对脑进行处理，检测齿状回中Ki-67(细胞增殖)、BrdU(细胞存活)、Doublecortin(年轻神经元产生)、固缩形态(细胞死亡)、激活的caspase-3(细胞凋亡)和Fluoro-Jade B(变性神经元)的表达。在雌性大鼠中，反复给予雌二醇降低了新神经元的存活率(与初始细胞增殖无关)，略微增加了细胞增殖，并减少了齿状回中总的细胞死亡。在雄性大鼠中，重复给予雌二醇对神经发生或细胞死亡没有显著影响。因此，我们发现成年大鼠海马神经发生和细胞凋亡对雌二醇的反应存在明显的性别差异，成年雌性大鼠比雄性大鼠对雌二醇的影响更敏感。(C)2008年由爱思唯尔有限公司代表IBRO出版。
Estradiol has been shown to have neuroprotective effects, and acute estradiol treatment enhances hippocampal neurogenesis in the female brain. However, little is known about the effects of repeated administration of estradiol on the female brain, or about the effects of estradiol on the male brain. Gonadectomized male and female adult rats were injected with 5-bromo-2-deoxyuridine (BrdU) (200 mg/kg), and then 24 h later were given subcutaneous injections of either estradiol benzoate (33 mu g/kg) or vehicle daily for 15 days. On day 16, animals were perfused and the brains processed to examine cells expressing Ki-67 (cell proliferation), BrdU (cell survival), doublecortin (young neuron production), pyknotic morphology (cell death), activated caspase-3 (apoptosis), and Fluoro-Jade B (degenerating neurons) in the dentate gyrus. In female rats, repeated administration of estradiol decreased the survival of new neurons (independent of any effects on initial cell proliferation), slightly increased cell proliferation, and decreased overall cell death in the dentate gyrus. In male rats, repeated administration of estradiol had no significant effect on neurogenesis or cell death. We therefore demonstrate a clear sex difference in the response to estradiol of hippocampal neurogenesis and apoptosis in adult rats, with adult females being more responsive to the effects of estradiol than males. (c) 2008 Published by Elsevier Ltd on behalf of IBRO.