Alzheimer's disease and other forms of cognitive decline are significantly more prevalent in post-menopausal women. Decreased estrogen levels, due to menopause or ovariectomy, may contribute to memory impairments and neurodegeneration. Another result of decreased estrogen levels is elevated luteinizing hormone (LH). Elevated LH after menopause/ovariectomy has been shown to impair cognition in both human and animal studies. Lowering LH levels rescues spatial memory in ovariectomized (ovx) rodents, yet the mechanisms of these effects are still unclear. Estrogens appear to exert some of their effects on memory by increasing levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. In these studies, we explored whether lowering LH may act by increasing BDNF. Ovx rats were treated with Antide, a gonadotropin releasing hormone receptor antagonist that lowers LH levels, or with estradiol. Both Antide and estradiol treatment enhanced spatial memory in ovx females. Both were found to be ineffective when a BDNF receptor antagonist was administered. Immunohistochemical analysis revealed that both Antide and estradiol increased BDNF expression in the hippocampus. Dendritic spine density on pyramidal cells in CA1 was unchanged by any treatment. These results provide evidence for a relationship between LH and BDNF in the hippocampus and demonstrate that estrogen-increasing and LH-lowering treatments may both require BDNF signaling in order to improve spatial memory.

中文翻译：

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卵巢切除术后降低黄体生成素水平可改善空间记忆：脑源性神经营养因子的可能作用。

阿尔茨海默氏病和其他形式的认知功能减退在绝经后妇女中更为普遍。由于绝经或卵巢切除术导致雌激素水平降低，可能会导致记忆力减退和神经退行性变。雌激素水平降低的另一个结果是促黄体生成激素（LH）升高。在人类和动物研究中，更年期/卵巢切除术后的LH升高已显示出对认知能力的损害。降低LH水平可以挽救卵巢切除（ovx）啮齿动物的空间记忆，但是这些作用的机制仍不清楚。雌激素似乎通过增加海马中脑源性神经营养因子（BDNF）的水平来发挥其对记忆的某些作用。在这些研究中，我们探讨了降低LH是否可能通过增加BDNF起作用。Ovx大鼠用Antide治疗，降低LH水平或与雌二醇的促性腺激素释放激素受体拮抗剂。Antide和雌二醇治疗均增强了ovx女性的空间记忆能力。当施用BDNF受体拮抗剂时，发现两者均无效。免疫组织化学分析显示，Antide和雌二醇均增加海马中BDNF的表达。任何处理均未改变CA1中锥体细胞的树突棘密度。这些结果为海马中LH和BDNF之间的关系提供了证据，并证明增加雌激素和降低LH的治疗都可能需要BDNF信号传导，以改善空间记忆。当施用BDNF受体拮抗剂时，发现两者均无效。免疫组织化学分析显示，Antide和雌二醇均增加海马中BDNF的表达。任何处理均未改变CA1中锥体细胞的树突棘密度。这些结果为海马中LH和BDNF之间的关系提供了证据，并证明增加雌激素和降低LH的治疗都可能需要BDNF信号传导，以改善空间记忆。当施用BDNF受体拮抗剂时，发现两者均无效。免疫组织化学分析显示，Antide和雌二醇均增加海马中BDNF的表达。任何处理均未改变CA1中锥体细胞的树突棘密度。这些结果为海马中LH和BDNF之间的关系提供了证据，并证明增加雌激素和降低LH的治疗都可能需要BDNF信号传导，以改善空间记忆。