title: Memory Impairment in Estrogen Receptor α Knockout Mice Through Accumulation of Amyloid-β Peptides.
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.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 52, Naesudong-ro, Heungdeok-gu, Cheongju, Chungbuk, 361-763, Republic of Korea.
authors.forename: Chul Ju
authors.initials: CJ
authors.lastname: Hwang
authors.forename: Hyung-Mun
authors.initials: HM
authors.lastname: Yun
authors.forename: Kyung-Ran
authors.initials: KR
authors.lastname: Park
authors.forename: Ju Kyung
authors.initials: JK
authors.lastname: Song
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Seo
authors.forename: Byung Kook
authors.initials: BK
authors.lastname: Hyun
authors.forename: Dong Young
authors.initials: DY
authors.lastname: Choi
authors.forename: Hwan-Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
authors.forename: Dae Yeun
authors.initials: DY
authors.lastname: Hwang
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D051546:Cyclooxygenase 2 / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008569:Memory Disorders / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015260:Neprilysin / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D047628:Estrogen Receptor alpha; D005904:Glial Fibrillary Acidic Protein; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015260:Neprilysin; D020780:Matrix Metalloproteinase 9