title: Enhanced activity of hippocampal BACE1 in a mouse model of postmenopausal memory deficits.
abstract: Ovarian hormone decline after menopause may influence cognitive performance and increase the risk for Alzheimer's disease (AD) in women. We have recently demonstrated that a combination of ovariectomy and chronic stress (OVX/stress) causes hippocampus-associated cognitive dysfunction in mice. In this study, we examined whether OVX/stress could affect the levels of AD-related molecules in the mouse hippocampus. Female ICR mice were ovariectomized or sham-operated, and then randomly divided into a daily restraint stress (21 days, 6 h/day) or non-stress group. Although OVX or stress alone did not affect beta-site amyloid precursor protein (APP)-cleaving enzyme-1 (BACE1) activity, OVX/stress increased activity in hippocampal CA1 and CA3 regions, compared with other groups. In contrast, OVX/stress did not affect gamma-secretase activity, Abeta(1-40), and phosphorylated-tau levels in the hippocampus. These findings suggest that a stressful life after menopause can influence the levels of AD-related molecules and that BACE1 is the most sensitive molecule for such a situation.
authors.affiliation: Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Fukuzaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takuma
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Himeno
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yoshida
authors.forename: Yoko
authors.initials: Y
authors.lastname: Funatsu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitahara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ibi
authors.forename: Koji
authors.initials: K
authors.lastname: Koike
authors.forename: Masaki
authors.initials: M
authors.lastname: Inoue
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology*; D051379:Mice; D008813:Mice, Inbred ICR; D010052:Ovariectomy / Q000379:methods; D017698:Postmenopause; D012149:Restraint, Physical / Q000379:methods; D013315:Stress, Psychological / Q000150:complications / Q000473:pathology; D013997:Time Factors
chemical_list: D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse