Memory Impairment in Estrogen Receptor α Knockout Mice Through Accumulation of Amyloid-β Peptides.
Memory Impairment in Estrogen Receptor α Knockout Mice Through Accumulation of Amyloid-β Peptides.
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DOI：
10.1007/s12035-014-8853-z
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发表时间：
2015-08
影响因子：
5.1
通讯作者：
Hong JT
中科院分区：
文献类型：
--
作者：
Hwang CJ;Yun HM;Park KR;Song JK;Seo HO;Hyun BK;Choi DY;Yoo HS;Oh KW;Hwang DY;Han SB;Hong JT
众所周知，雌激素可以减少阿尔茨海默病（AD）的发展。然而，确切的机制尚不清楚。我们在雌激素缺乏模型中研究了雌激素是否会增加淀粉样蛋白β (Aβ)的降解并影响Aβ诱导的记忆障碍。雌性激素受体α (ERα)敲除小鼠和野生型小鼠在脑室内注射Aβ (300 pmol) 2周。采用Morris水迷宫测验和被动回避测验评估认知功能。此外，采用Western blot、免疫染色、免疫荧光染色、ELISA、酶活性等方法检测ERα敲除小鼠脑内Aβ的沉积程度。在我们目前的研究中，Aβ在ERα敲除小鼠的大脑中积累更多，并大大加重了记忆障碍和神经胶质激活以及神经源性炎症。提示雌激素可能通过刺激Aβ降解、下调神经源性炎症和淀粉样蛋白形成来保护记忆损伤。本文的在线版本（doi:10.1007/s12035-014-8853-z）含有补充资料，仅供授权用户使用。
Estrogen has been known to reduce the development of Alzheimer’s disease (AD). However, exact mechanisms are not clear. We investigated whether estrogen can increase amyloid-beta (Aβ) degradation and affects Aβ-induced memory impairment in an estrogen deficiency model. Estrogen receptor alpha (ERα) knockout mice and wild-type mice were intracerebroventricular (ICV) infused with Aβ (300 pmol) for 2 weeks. Cognitive function was then assessed by the Morris water maze test and passive avoidance test. In addition, Western blot analysis, immunostaining, immunofluorescence staining, ELISA, and enzyme activity assays were used to examine the degree of Aβ deposition in the brains of ERα knockout mice. In our present study, Aβ was accumulated more in the ERα knockout mice brain and greatly worsened memory impairment and glial activation as well as neurogenic inflammation. These results suggest that estrogen may protect memory impairment by stimulating the degradation of Aβ and down-regulate neurogenic inflammation as well as amyloidogenesis. The online version of this article (doi:10.1007/s12035-014-8853-z) contains supplementary material, which is available to authorized users.