Selective Estrogen Receptor Modulators Decrease Reactive Astrogliosis in the Injured Brain: Effects of Aging and Prolonged Depletion of Ovarian Hormones
Selective Estrogen Receptor Modulators Decrease Reactive Astrogliosis in the Injured Brain: Effects of Aging and Prolonged Depletion of Ovarian Hormones
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DOI：
10.1210/en.2009-0352
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发表时间：
2009-11-01
期刊：
影响因子：
4.8
通讯作者：
Garcia-Segura, Luis M.
中科院分区：
文献类型：
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作者：
Barreto, George;Santos-Galindo, Maria;Garcia-Segura, Luis M.
脑损伤后，星形胶质细胞获得反应性表型，其特征在于一系列形态和分子修饰，包括细胞骨架蛋白波形蛋白的表达。以前的研究表明，雌二醇下调反应性星形胶质细胞增生。在这项研究中，我们评估了雷洛昔芬和他莫昔芬，两种选择性雌激素受体调节剂，是否具有类似于雌二醇在星形胶质细胞中的作用。我们还评估了年龄和卵巢切除术后雌激素治疗的时机是否会影响雌激素化合物的作用。研究了四组动物：1）年轻大鼠，在2月龄时切除卵巢; 2）中年大鼠，在8月龄时切除卵巢; 3）老年大鼠，在18月龄时切除卵巢; 4）老年大鼠，在2月龄时切除卵巢，在18月龄时进行假手术。卵巢切除术或假手术后15天，动物接受刺伤性脑损伤和雌激素化合物治疗。损伤后波形蛋白免疫反应阳性星形胶质细胞的数量显着较高的老年大鼠海马长期卵巢切除术后，与老年动物短期卵巢切除术后和中年大鼠。此外，反应性星形胶质细胞在两组老年动物比年轻的动物更多。尽管存在这些差异，雌激素化合物仍减少了所有动物组的反应性星形胶质细胞增生。这些结果表明，雌二醇，雷洛昔芬，他莫昔芬是控制星形胶质细胞增生在年轻和老年人和卵巢激素长期耗尽后的潜在候选人。（内分泌学150：5010 - 5015，2009）
After brain injury, astrocytes acquire a reactive phenotype characterized by a series of morphological and molecular modifications, including the expression of the cytoskeletal protein vimentin. Previous studies have shown that estradiol down-regulates reactive astrogliosis. In this study we assessed whether raloxifene and tamoxifen, two selective estrogen receptor modulators, have effects similar to estradiol in astrocytes. We also assessed whether aging and the timing of estrogenic therapy after ovariectomy influence the action of the estrogenic compounds. Four groups of animals were studied: 1) young rats, ovariectomized at 2 months of age; 2) middle-aged rats, ovariectomized at 8 months of age; 3) aged rats, ovariectomized at 18 months of age; and 4) aged rats, ovariectomized at 2 months and sham operated at 18 months of age. Fifteen days after ovariectomy or sham surgery, animals received a stab wound brain injury and the treatment with the estrogenic compounds. The number of vimentin-immunoreactive astrocytes after injury was significantly higher in the hippocampus of aged rats after a long-term ovariectomy compared with aged animals after a short-term ovariectomy and middle-aged rats. In addition, reactive astrocytes were more numerous in the two groups of aged animals than in young animals. Despite these differences, the estrogenic compounds reduced reactive astrogliosis in all animal groups. These findings indicate that estradiol, raloxifene, and tamoxifen are potential candidates for the control of astrogliosis in young and older individuals and after a prolonged depletion of ovarian hormones. (Endocrinology 150: 5010-5015, 2009)