In the present study, to determine whether aging could increase the vulnerability of the brain to estrogen withdrawal-induced mitochondrial dysfunction, we measured the cytochrome c oxidase (COX) activity and mitochondrial adenosine triphosphate (ATP) content in hippocampi of 2 groups of ovariectomized (OVX) Wistar rats aged 2 months (young) and 9 months (middle-aged), respectively. In addition, effects of genistein and estradiol benzoate (EB) were tested also. We observed only a transient alteration of COX activity and mitochondrial ATP content in hippocampi of young OVX rats but a prolonged lowering of COX activity and mitochondrial ATP content in hippocampi of middle-aged OVX rats. This suggested that with aging compensatory mechanisms of mitochondrial function were attenuated, thus exacerbated estrogen withdrawal-induced mitochondrial dysfunction in hippocampi. Significantly, EB/genistein treatment reversed this estrogen withdrawal-induced mitochondrial dysfunction in both young and middle-aged rats suggesting that genistein may be used as a substitute for estradiol to prevent age-related disease such as Alzheimer's disease in post-menopausal females.

中文翻译：

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随着年龄的增长，大脑对雌激素戒断引起的线粒体功能障碍的脆弱性增加。

在本研究中，为了确定衰老是否会增加大脑对雌激素戒断诱导的线粒体功能障碍的脆弱性，我们测量了 2 组卵巢切除组海马中细胞色素 c 氧化酶 (COX) 活性和线粒体三磷酸腺苷 (ATP) 含量。 OVX) 分别为 2 个月大（年轻）和 9 个月大（中年）的 Wistar 大鼠。此外，还测试了染料木黄酮和雌二醇苯甲酸酯 (EB) 的作用。我们仅观察到年轻 OVX 大鼠海马中 COX 活性和线粒体 ATP 含量的短暂改变，但观察到中年 OVX 大鼠海马中 COX 活性和线粒体 ATP 含量的长期降低。这表明随着衰老的线粒体功能代偿机制减弱，因此加剧了雌激素戒断诱导的海马线粒体功能障碍。值得注意的是，EB/染料木黄酮治疗在年轻和中年大鼠中逆转了这种雌激素戒断诱导的线粒体功能障碍，表明染料木黄酮可用作雌二醇的替代品，以预防绝经后女性的阿尔茨海默病等年龄相关疾病。