Estrogen decreases zinc transporter 3 expression and synaptic vesicle zinc levels in mouse brain
Estrogen decreases zinc transporter 3 expression and synaptic vesicle zinc levels in mouse brain
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DOI：
10.1074/jbc.m309730200
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发表时间：
2004-03-05
影响因子：
4.8
通讯作者：
Koh, JY
中科院分区：
文献类型：
--
作者：
Lee, JY;Kim, JH;Koh, JY
以前的研究表明，女性性激素调节突触锌水平，这可能会影响淀粉样斑块的形成和阿尔茨海默病的进展。我们研究了卵巢切除和雌激素补充对大脑中突触锌和锌转运蛋白Znt 3水平的影响。对5月龄小鼠进行卵巢切除术，2周后，植入含有载体、低剂量（0.18 mg/丸）或高剂量（0.72 mg）17 β-雌二醇的丸。4周后，将动物断头，收集血液和脑用于分析。血液分析表明，雌激素植入剂以剂量依赖性方式改变血浆雌激素水平。脑组织分析表明，卵巢切除提高海马突触囊泡锌水平，而雌激素替代降低这些锌水平。Western印迹显示，在大脑中的Znt 3水平与突触锌水平平行调制，而没有变化，检测到Znt 3 mRNA的水平，由北方印迹和逆转录酶-PCR分析确定。然而，调节Znt 3水平的衔接蛋白复合物（AP）-3的δ亚基的mRNA水平被雌激素消耗或替代改变。这些数据表明，雌激素改变雌性小鼠的Znt 3和突触囊泡锌的水平，可能是通过改变AP-3 δ的表达。由于突触锌可能在急性脑损伤中的神经元死亡以及阿尔茨海默病中的斑块形成中发挥关键作用，并且由于雌激素可能在这两种情况下都是有益的，因此我们的研究结果可能为雌激素对大脑的影响提供新的见解。
Previous studies suggest that female sex hormones modulate synaptic zinc levels, which may influence amyloid plaque formation and Alzheimer's disease progression. We examined the effects of ovariectomy and estrogen supplement on the levels of synaptic zinc and zinc transporter protein Znt3 in the brain. Ovariectomy was performed on 5-month-old mice, and 2 weeks later, pellets containing vehicle, low (0.18 mg/pellet), or high dose (0.72 mg) 17beta-estradiol were implanted. After 4 weeks, animals were decapitated, and blood and brain were collected for analysis. Blood analysis indicated that estrogen implants altered plasma estrogen levels in a dose-dependent manner. Analysis of brain tissue showed that ovariectomy raised hippocampal synaptic vesicle zinc levels, whereas estrogen replacement lowered these zinc levels. Western blots revealed that Znt3 levels in the brain were modulated in parallel with synaptic zinc levels, whereas no change was detected in the levels of Znt3 mRNA, as determined by Northern blot and reverse transcriptase-PCR analysis. However, mRNA levels of the delta subunit of adaptor protein complex (AP)-3, which modulates the level of Znt3 levels, were altered by estrogen depletion or replacement. These data demonstrate that estrogen alters the levels of Znt3 and synaptic vesicle zinc in female mice, probably through changing AP-3 delta expression. Since synaptic zinc may play a key role in neuronal death in acute brain injury as well as in plaque formation in Alzheimer's disease, and since estrogen may be beneficial in both conditions, our results may provide new insights into the effects of estrogen on the brain.