High serum androstenedione levels correlate with impaired memory in the surgically menopausal rat: a replication and new findings
High serum androstenedione levels correlate with impaired memory in the surgically menopausal rat: a replication and new findings
复制标题
DOI：
10.1111/j.1460-9568.2012.08194.x
复制
发表时间：
2012-10-01
影响因子：
3.4
通讯作者：
Bimonte-Nelson, Heather A.
中科院分区：
文献类型：
--
作者：
Camp, Bryan W.;Gerson, Julia E.;Bimonte-Nelson, Heather A.
女性自然绝经后，雄烯二酮成为残留卵泡耗竭卵巢分泌的主要激素。在两项独立的研究中，在经历卵巢卵泡耗竭的啮齿动物中，我们发现较高的内源性血清雄烯二酮水平与工作记忆错误增加相关。这导致了较高的雄烯二酮水平损害记忆的假设。目前的研究直接验证了这一假设，研究了啮齿动物外源性雄烯二酮给药的认知效应。中年卵巢切除大鼠接受载体或两种剂量的雄烯二酮之一。采用空间工作记忆和参考记忆迷宫组合，包括水-桡臂迷宫、Morris水迷宫和延迟匹配任务。雄烯二酮在最高剂量时会损害参考记忆以及维持记忆需求升高时的表现能力。这对于一个空间信息项目的高时间需求记忆保持以及处理多个空间工作记忆信息项目的能力都是真实的。我们测量了谷氨酸脱羧酶（GAD）蛋白在多个脑区，以确定是否γ-氨基丁酸（GABA）系统与雄烯二酮诱导的记忆障碍。结果表明，较高的内嗅皮质GAD水平与较差的MM表现相关，无论雄烯二酮治疗。这些发现表明，雄烯二酮，卵泡耗竭卵巢产生的主要激素，是有害的工作记忆，参考记忆和记忆保持。此外，虽然空间参考记忆能力可能与GABA能系统有关，但至少在本研究中使用的剂量下，雄烯二酮给药似乎不会改变空间参考记忆能力。
After natural menopause in women, androstenedione becomes the primary hormone secreted by the residual follicle-depleted ovaries. In two independent studies, in rodents that had undergone ovarian follicular depletion, we found that higher endogenous serum androstenedione levels correlated with increased working memory errors. This led to the hypothesis that higher androstenedione levels impair memory. The current study directly tested this hypothesis, examining the cognitive effects of exogenous androstenedione administration in rodents. Middle-aged ovariectomised rats received vehicle or one of two doses of androstenedione. Rats were tested on a spatial working and reference memory maze battery including the water-radial arm maze, Morris water maze (MM) and delay match-to-sample task. Androstenedione at the highest dose impaired reference memory as well as the ability to maintain performance as memory demand was elevated. This was true for both high temporal demand memory retention of one item of spatial information, as well as the ability to handle multiple items of spatial working memory information. We measured glutamic acid decarboxylase (GAD) protein in multiple brain regions to determine whether the gamma-aminobutyric acid (GABA) system relates to androstenedione-induced memory impairments. Results showed that higher entorhinal cortex GAD levels were correlated with worse MM performance, irrespective of androstenedione treatment. These findings suggest that androstenedione, the main hormone produced by the follicle-depleted ovary, is detrimental to working memory, reference memory and memory retention. Furthermore, while spatial reference memory performance might be related to the GABAergic system, it does not appear to be altered with androstenedione administration, at least at the doses used in the current study.