Long-term ovarian hormone deprivation alters the ability of subsequent oestradiol replacement to regulate choline acetyltransferase protein levels in the hippocampus and prefrontal cortex of middle-aged rats
Long-term ovarian hormone deprivation alters the ability of subsequent oestradiol replacement to regulate choline acetyltransferase protein levels in the hippocampus and prefrontal cortex of middle-aged rats
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DOI：
10.1111/j.1365-2826.2008.01752.x
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发表时间：
2008-08-01
影响因子：
3.2
通讯作者：
Daniel, J. M.
中科院分区：
文献类型：
--
作者：
Bohacek, J.;Bearl, A. M.;Daniel, J. M.
雌激素替代疗法在预防或延缓与年龄相关的认知能力下降方面的作用存在争议。治疗成功可能主要取决于卵巢功能停止后开始治疗的时间。本研究旨在评估中年大鼠雌二醇调节胆碱能系统的能力是否取决于卵巢切除术后开始治疗的时间。使用蛋白质印迹法测量海马体和前额皮质 (PFC) 中胆碱乙酰转移酶 (ChAT) 的蛋白质水平，这两个区域都是认知功能的重要区域。在初步实验中，我们确定了通过植入胶囊递送的雌二醇对年轻成年动物海马和 PFC 中 ChAT 水平的影响。在第二个实验中，我们测试了相同雌二醇治疗模式对 15 个月大的中年大鼠 ChAT 蛋白的影响，这些大鼠在 10 个月或 15 个月时已切除卵巢。在这两个实验中，大鼠在接受植入物 10 天后被处死，并测量 ChAT 蛋白水平。在年轻成年和中年动物中，与胆固醇对照治疗相比，卵巢切除后立即开始的雌二醇治疗显着增加了海马中的 ChAT 水平，但没有增加前额皮质中的 ChAT 水平。然而，当卵巢切除术后 5 个月开始雌二醇治疗时，它未能显着增加海马中的 ChAT 水平，但在 PFC 中却有所增加。这些数据表明，在长期剥夺卵巢激素后，随后的雌二醇治疗调节 ChAT 蛋白水平的能力会以位点特异性方式发生改变。
The role of oestrogen replacement therapy in preventing or delaying age-associated cognitive decline is controversial. Therapy success may critically depend on the time of treatment initiation following cessation of ovarian function. The present study aimed to assess, in middle-aged rats, whether the ability of oestradiol to modulate the cholinergic system depends on the timing of treatment initiation following ovariectomy. Using western blotting, protein levels of choline acetyltransferase (ChAT) were measured in the hippocampus and prefrontal cortex (PFC), which are both important areas with respect to cognitive function. In an initial experiment, we established the effects of oestradiol delivered via implanted capsules on ChAT levels in the hippocampus and PFC of young adult animals. In a second experiment, we tested the ability of the same oestradiol treatment paradigm to affect ChAT protein in 15-month-old middle-aged rats that had been ovariectomised either at the age of 10 months or at 15 months. In both experiments, rats were sacrificed 10 days after receiving implants and ChAT protein levels were measured. In both young adult and middle-aged animals, oestradiol treatment initiated immediately after ovariectomy significantly increased ChAT levels in the hippocampus but not in the PFC compared to cholesterol control treatment. However, when oestradiol treatment was initiated 5 months after ovariectomy, it,failed to significantly increase ChAT levels in the hippocampus, but did so in the PFC. These data indicate that, after prolonged ovarian hormone deprivation, the ability of subsequent oestradiol treatment to modulate ChAT protein levels is altered in a site-specific manner.