Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-014-8853-z) contains supplementary material, which is available to authorized users.
Highlights
MethodsEstrogen is important in the maintenance of normal brain function
Hong (*) College of Pharmacy, Medical Research Center, Chungbuk National University, 12, Gaeshin-dong, Heungdeok-gu, Cheongju, Chungbuk 361-763, Republic of Korea e-mail: jinthong@chungbuk.ac.kr 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
We investigated whether the knockout of ERα could down-regulate neprilysin and other Aβ-degrading enzyme expressions and activities, diminishing Aβscavenging activity leading to the enhancement of neuronal cell death and memory impairment in Aβ42-infused ERα knockout mice
Summary
MethodsEstrogen is important in the maintenance of normal brain function. It interacts with many different receptors including alpha and beta estrogen receptors, both of them highly expressed in the hippocampus and cortex, the two brain regions most implicated in the develop of Alzheimer’s disease (AD) [1]. Western blot data for BAX and caspase-3(a proapoptotic protein) expression (Fig. 2c) were increased in Aβ1–42-infused ERα knockout mice brain compared to the expression in Aβ1–42-infused C57BL/6 wild-type mice brain. Western blot analysis revealed that APP and BACE1 expression were significantly higher in the brains of Aβ1–42-infused ERα knockout mice compared to Aβ1–42-infused C57BL/6 wild-type mice
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