Tonic Premarin dose-dependently enhances memory, affects neurotrophin protein levels and alters gene expression in middle-aged rats.
Tonic Premarin dose-dependently enhances memory, affects neurotrophin protein levels and alters gene expression in middle-aged rats.
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DOI：
10.1016/j.neurobiolaging.2009.09.005
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发表时间：
2011-04
影响因子：
4.2
通讯作者：
Bimonte-Nelson HA
中科院分区：
文献类型：
--
作者：
Engler-Chiurazzi E;Tsang C;Nonnenmacher S;Liang WS;Corneveaux JJ;Prokai L;Huentelman MJ;Bimonte-Nelson HA
自 1942 年以来，Premarin™ 是激素治疗中最常用的雌激素成分。当前的研究是首次在动物模型中检验补品 Premarin 治疗的认知效果。中年卵巢切除 (Ovx) 大鼠接受赋形剂或三种剂量的倍力马之一（每天 12、24 或 36 μg）。老鼠在空间工作和参考记忆迷宫电池上进行了测试。中剂量和高剂量的倍力马都能增强记忆力，而低剂量的倍力力会损害学习和记忆力。与血清激素水平的相关性表明，随着雌酮：17β-雌二醇比例的增加，动物往往表现出更好的工作记忆表现。结合剂量特异性雌激素谱的解离，结果表明，在 17β-雌二醇浓度高于 Ovx 水平的情况下，较高水平的雌酮可能有利于记忆。此外，倍美力对 BDNF 和 NGF 蛋白水平产生剂量和脑区域特异性影响，其中扣带皮层和鼻周皮质的变化最显着。海马基因表达谱表明，普力马诱导的与可塑性和认知相关的基因发生了显着的转录变化。这些发现表明，倍美力可以影响记忆和大脑，并且剂量应被视为可能影响认知结果的方向和功效的临床相关因素。
Premarin™ is the most commonly prescribed estrogenic component of hormone therapy, given since 1942. The current study is the first examining cognitive effects of tonic Premarin treatment in an animal model. Middle-aged ovariectomized (Ovx) rats received vehicle or one of three doses of Premarin (12, 24 or 36 μg daily). Rats were tested on a spatial working and reference memory maze battery. Both Medium- and High- dose Premarin enhanced memory retention, while Low-dose Premarin impaired learning and memory retention. Correlations with serum hormone levels showed that as the ratio of estrone:17β-estradiol increased, animals tended to show better working memory performance. Taken together with the dissociation of dose-specific estrogenic profiles, results suggest that higher levels of estrone, in the presence of 17β-estradiol concentrations higher than that of Ovx levels, may be beneficial for memory. Moreover, Premarin exerted dose and brain-region specific effects on BDNF and NGF protein levels, with most marked changes in cingulate and perirhinal cortices. Hippocampal gene expression profiling demonstrated significant Premarin-induced transcriptional changes in genes linked to plasticity and cognition. These findings indicate that Premarin can impact memory and the brain, and that dosing should be recognized as a clinically relevant factor possibly affecting the direction and efficacy of cognitive outcome.
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影响因子：
4.2
作者：
Bimonte, HA;Nelson, ME;Granholm, ACE
通讯作者：
Granholm, ACE
影响因子：
64.8
作者：
Brakeman, PR;Lanahan, AA;Worley, PF
通讯作者：
Worley, PF
影响因子：
7.2
作者：
Almeida, OP;Lautenschlager, N;Flicker, L
通讯作者：
Flicker, L
DOI：
10.1111/j.1532-5415.1999.tb07427.x
发表时间：
1999-11-01
影响因子：
6.3
作者：
Barrett-Connor, E;Goodman-Gruen, D
通讯作者：
Goodman-Gruen, D
影响因子：
3.4
作者：
Bimonte-Nelson, Heather A.;Francis, Kevin R.;Granholm, Ann-Charlotte
通讯作者：
Granholm, Ann-Charlotte