雌激素对大鼠大脑皮层器官外植体缺血性细胞死亡和雌激素受体 mRNA 表达的性别特异性影响

IF 1.7 Q3 CLINICAL NEUROLOGY
Amanda L. Trout , Christopher J McLouth , Jenne M. Westberry , Tomoko Sengoku , Melinda E. Wilson
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引用次数: 0

摘要

雌激素,如具有生物活性的 17-β 雌二醇(E2),不仅能调节成年人的生殖行为,还能影响雌性和雄性的神经发育和神经保护。根据治疗时机和浓度的不同,E2 对雌性和雄性中风啮齿动物模型具有神经保护作用。体内研究表明,E2 可通过 ERα 部分介导这种神经保护作用,尤其是在大脑皮层。体外研究利用化学诱导的缺血性损伤对雌雄啮齿动物的大脑皮层外植体进行了研究,结果表明ERα或ERβ信号传导是E2保护作用的必要介导因素。由于我们知道E2治疗的时间和浓度可能具有性别特异性,因此我们研究了当从出生后第3-4天的大鼠中分别分离出雌性和雄性皮层外植体时,E2(1 nM)是否能介导神经保护作用。我们比较了完整皮层在出生后早期发育过程中ERα、ERβ和AR mRNA表达的基础水平变化,以及皮层外植体在体外相应天数(DIV)的变化。在缺血损伤 7 DIV 后,比较了雌性和雄性皮层外植体的细胞死亡及 ERα、ERβ 和 AR mRNA 表达。我们提供的证据表明,E2-介导的保护作用在雌性而非雄性大鼠的离体皮质外植体中得以维持。这些结果表明,E2-介导的大脑皮层保护作用受性别影响,并支持对缺血损伤后的雌性和雄性进行不同处理的数据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Estrogen’s sex-specific effects on ischemic cell death and estrogen receptor mRNA expression in rat cortical organotypic explants

Estrogens, such as the biologically active 17-β estradiol (E2), regulate not only reproductive behaviors in adults, but also influence neurodevelopment and neuroprotection in both females and males. E2, contingent upon the timing and concentration of the therapy, is neuroprotective in female and male rodent models of stroke. In Vivo studies suggest that E2 may partially mediate this neuroprotection, particularly in the cortex, via ERα. In Vitro studies, utilizing a chemically induced ischemic injury in cortical explants from both sexes, suggest that ERα or ERβ signaling is needed to mediate the E2 protection. Since we know that the timing and concentration of E2 therapy may be sex-specific, we examined if E2 (1 nM) mediates neuroprotection when female and male cortical explants are separately isolated from postnatal day (PND) 3–4 rat. Changes in basal levels ERα, ERβ, and AR mRNA expression are compared across early post-natal development in the intact cortex and the corresponding days in vitro (DIV) for cortical explants. Following ischemic injury at 7 DIV, cell death and ERα, ERβ and AR mRNA expression was compared in female and male cortical explants. We provide evidence that E2-mediated protection is maintained in isolated cortical explants from females, but not male rats. In female cortical explants, the E2-mediated protection at 24 h occurs secondarily to a blunted transient increase in ERα mRNA at 12 h. These results suggest that cortical E2-mediated protection is influenced by sex and supports data to differentially treat females and males following ischemic injury.

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来源期刊
Aging brain
Aging brain Neuroscience (General), Geriatrics and Gerontology
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