Enhanced activity of hippocampal BACE1 in a mouse model of postmenopausal memory deficits
- 作者：Emiko Fukuzaki ; Kazuhiro Takuma ; Yukiko Himeno ; Shigeru Yoshida ; Yoko Funatsu ; Yuko Kitahara ; Hiroyuki Mizoguchi ; Daisuke Ibi ; Koji Koike ; Masaki Inoue ; Kiyofumi Yamada
- 关键词：Ovariectomy ; Alzheimer's disease ; BACE ; Amyloid β ; peptide ; Phosphorylated-tau
- 刊名：Neuroscience Letters
- 出版年：2008
- 期刊代码：52_03043940
- 类别：neu
- 出版时间：12 March 2008
- 卷：433
- 期：2
- 页码：141-145
- 文件大小：194 K
摘要
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 β-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 γ-secretase activity, Aβ1-40, 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.