A component of Premarin(®) enhances multiple cognitive functions and influences nicotinic receptor expression.
A component of Premarin(®) enhances multiple cognitive functions and influences nicotinic receptor expression.
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DOI：
10.1016/j.yhbeh.2010.09.002
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发表时间：
2010-11
影响因子：
3.5
通讯作者：
Bimonte-Nelson, Heather A.
中科院分区：
文献类型：
--
作者：
Talboom, Joshua S.;Engler-Chiurazzi, Elizabeth B.;Whiteaker, Paul;Simard, Alain R.;Lukas, Ronald;Acosta, Jazmin I.;Prokai, Laszlo;Bimonte-Nelson, Heather A.
关键词：
在女性中，绝经期卵巢激素丢失与认知能力下降有关，一些研究表明含雌激素的激素治疗（HT）可以减轻这些影响。最近，妇女健康倡议的研究发现，共轭马雌激素，最常用的处方HT，不有利于认知。已在体外评价了结合的马雌激素（商品名Premarin®）的分离组分，其中Δ 8，9-脱氢雌酮（Δ 8 E1）和马烯雌酮显示出最强的神经保护作用。尚未评估Δ 8 E1或马雌激素是否影响认知或胆碱能系统，胆碱能系统受其他雌激素影响并已知调节认知。在这里，在中年，卵巢切除大鼠，我们评估了Δ 8 E1和马烯雌酮治疗对认知电池和胆碱能烟碱受体（nAChR）的影响。具体而言，我们使用125 I标记的地棘蛙素结合来测定含有4个α和2个β亚基的神经元烟碱受体（α4β2-nAChR），因为这种烟碱受体亚型先前已被证明对其他雌激素敏感。Δ 8 E1增强了空间工作记忆、最近记忆和参考记忆。Δ 8 E1还降低海马和内嗅皮层α4β2-nAChR的表达，这与空间参考记忆成绩有关。马烯雌酚处理不影响大鼠的空间记忆或α4β2-nAChR表达。两种雌激素均不影响86 Rb+外排，表明对人α4β2 nAChR功能缺乏直接作用。这两种雌激素影响阴道涂片，子宫重量，血清促黄体激素水平，类似于经典的雌激素。研究结果表明，特定的分离倍美力®组分在影响认知和nAChR表达的能力方面存在差异。与其他人的作品显示Δ 8 E1在与更年期相关的健康相关问题的几个维度上诱导的益处一起，这将Δ 8 E1确定为一种新的途径，可以作为HT的潜在成分进行研究，可能有益于衰老期间的大脑健康和功能。
In women, ovarian hormone loss at menopause has been related to cognitive decline, and some studies suggest that estrogen-containing hormone therapy (HT) can mitigate these effects. Recently, the Women’s Health Initiative study found that conjugated equine estrogens, the most commonly prescribed HT, do not benefit cognition. Isolated components of conjugated equine estrogens (tradename Premarin®) have been evaluated in vitro, with Δ8,9-dehydroestrone (Δ8E1) and equilin showing the strongest neuroprotective profiles. It has not been evaluated whether Δ8E1 or equilin impact cognition or the cholinergic system, which is affected by other estrogens and known to modulate cognition. Here, in middle-aged, ovariectomized rats, we evaluated the effects of Δ8E1 and equilin treatments on a cognitive battery and cholinergic nicotinic receptors (nAChR). Specifically, we used 125I-labeled epibatidine binding to assay the neuronal nicotinic receptor containing 4α and 2β subunits (α4β2-nAChR), since this nicotinic receptor subtype has been shown previously to be sensitive to other estrogens. Δ8E1 enhanced spatial working, recent and reference memory. Δ8E1 also decreased hippocampal and entorhinal cortex α4β2-nAChR expression, which was related to spatial reference memory performance. Equilin treatment did not affect spatial memory or rat α4β2-nAChR expression. Neither estrogen impacted 86Rb+ efflux, indicating lack of direct action on human α4β2 nAChR function. Both estrogens influenced vaginal smear profiles, uterine weights, and serum luteinizing hormone levels, analogous to classic estrogens. The findings indicate that specific isolated Premarin® components differ in their ability to affect cognition and nAChR expression. Taken with the works of others showing Δ8E1-induced benefits on several dimensions of health-related concerns associated with menopause, this identifies Δ8E1 as a new avenue to be investigated as a potential component of HT that may benefit brain health and function during aging.
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影响因子：
4.1
作者：
Cardoso, CC;Pereira, RTS;Abdalla, FMF
通讯作者：
Abdalla, FMF
影响因子：
3.3
作者：
Daniel, JM;Hulst, JL;Lee, CD
通讯作者：
Lee, CD
影响因子：
3.2
作者：
Bohacek, J.;Bearl, A. M.;Daniel, J. M.
通讯作者：
Daniel, J. M.
影响因子：
3.5
作者：
Daniel, JM;Fader, AJ;Dohanich, GP
通讯作者：
Dohanich, GP
影响因子：
4.2
作者：
Bimonte, HA;Nelson, ME;Granholm, ACE
通讯作者：
Granholm, ACE