Memory Impairment in Estrogen Receptor α Knockout Mice Through Accumulation of Amyloid-β Peptides

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 (A beta) degradation and affects A beta-induced memory impairment in an estrogen deficiency model. Estrogen receptor alpha (ER alpha) knockout mice and wild-type mice were intracerebroventricular (ICV) infused with A beta (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 A beta deposition in the brains of ER alpha knockout mice. In our present study, A beta was accumulated more in the ER alpha 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 A beta and down-regulate neurogenic inflammation as well as amyloidogenesis.