A Quantification of the Injury-Induced Changes in Central Aromatase, Oestrogenic Milieu and Steroid Receptor Expression in the Zebra Finch.
A Quantification of the Injury-Induced Changes in Central Aromatase, Oestrogenic Milieu and Steroid Receptor Expression in the Zebra Finch.
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DOI：
10.1111/jne.12348
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发表时间：
2016-02
影响因子：
3.2
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中科院分区：
文献类型：
--
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在鸣禽和哺乳动物中，脑损伤导致星形胶质细胞芳香化酶（雌激素合成酶）表达上调。由此产生的，推测的神经雌二醇（E2）的合成具有神经保护作用，包括减少神经变性，神经炎症和细胞凋亡。开发利用雌激素神经保护治疗神经创伤的治疗工具需要精确定量脑损伤后神经芳香化酶和雌二醇的内源性变化。令人惊讶的是，脑损伤后神经雌激素的预期增加尚未得到证实。此外，我们刚刚开始解开中枢合成雌二醇的保护作用背后的机制。在目前的研究中，芳香化酶免疫蛋白，神经雌二醇和类固醇受体mRNA的水平进行了定量的成年男性和女性斑胸草雀48小时后，单侧穿透性脑损伤。与未受伤的大脑半球相比，芳香酶和雌二醇在受伤的大脑半球中均上调，这首次表明损伤后神经雌二醇水平大幅增加。我们没有检测到损伤对雌激素受体（ER）-α、ER-β或GPER-1的mRNA表达的影响，但观察到相对于对侧未损伤半球，损伤叶中雄激素受体（AR）转录显著降低。我们的结论是，机械损伤导致局部芳构化的急剧增加，由此产生的高水平的中央雌二醇可用于调节类固醇敏感的目标。使用受体检测和/或时间点的替代方法的研究可能是必要的，以了解在这种动物模型中诱导雌激素合成的神经保护作用的机制的完整套件。
In songbirds and mammals, brain injury results in the upregulation of aromatase (estrogen synthase) expression in astroglia. The resulting, presumed synthesis of neural estradiol (E2) has neuroprotective effects including a decrease in neurodegeneration, neuroinflammation, and apoptosis. The development of therapeutic tools that exploit estrogenic neuroprotection in the treatment of neurotrauma require a precise quantification of the endogenous changes in neural aromatase and estradiol following brain injury. Surprisingly, the expected increase in neural estrogens following brain injury has not been demonstrated. Further, we are just beginning to unravel the mechanisms behind the protective effects of centrally synthesized estradiol. In the current study, levels of aromatase immunoprotein, neural estradiol, and steroid receptor mRNA were quantified in adult male and female zebra finches 48 hours following a unilateral penetrating brain injury. Both aromatase and estradiol were upregulated in the injured hemisphere of the brain compared to the uninjured hemisphere, demonstrating, for the first time, a robust increase in neural estradiol levels following injury. We did not detect an effect of injury on mRNA expression of the estrogen receptors (ER)-α, ER-β, or GPER-1, but observed a significant decrease in androgen receptor (AR) transcription in the injured lobe relative to the contralateral uninjured hemisphere. We conclude that mechanical damage causes a dramatic increase in local aromatization, and the resultant high levels of central estradiol are available to modulate steroid sensitive targets. Studies using alternate methods of receptor detection and/or time points may be necessary to understand the complete suite of mechanisms underlying the neuroprotective effects of induced estrogen synthesis in this animal model.
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影响因子：
4.1
作者：
Karki, Pratap;Smith, Keisha;Johnson, James, Jr.;Lee, Eunsook
通讯作者：
Lee, Eunsook
影响因子：
3.2
作者：
Remage-Healey L;Oyama RK;Schlinger BA
通讯作者：
Schlinger BA
影响因子：
3.5
作者：
Duncan, Kelli A.;Walters, Bradley J.;Saldanha, Colin J.
通讯作者：
Saldanha, Colin J.
影响因子：
3.6
作者：
Buchanan, CD;Mahesh, VB;Brann, DW
通讯作者：
Brann, DW
影响因子：
2.9
作者：
Chao A;Schlinger BA;Remage-Healey L
通讯作者：
Remage-Healey L