Enhanced activity of hippocampal BACE1 in a mouse model of postmenopausal memory deficits.
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.
Fukuzaki
Emiko
E
Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, Japan.
Takuma
Kazuhiro
K
Himeno
Yukiko
Y
Yoshida
Shigeru
S
Funatsu
Yoko
Y
Kitahara
Yuko
Y
Mizoguchi
Hiroyuki
H
Ibi
Daisuke
D
Koike
Koji
K
Inoue
Masaki
M
Yamada
Kiyofumi
K
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
D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse