Estrogen deficiency exacerbates A β-induced memory impairment through enhancement of neuroinflammation, amylodogenesis and NF-ĸB activation in ovariectomized mice

Publication date: Available online 18 May 2018 Source:Brain, Behavior, and Immunity Author(s): Jaesuk Yun, In Jun Yeo, Chul Ju Hwang, Dong-Young Choi, Hyung-Sik Im, Ji Youg Kim, Won Rak Choi, Myung Hee Jung, Sang-Bae Han, Jin Tae Hong Estrogen is well known to have a preventative effect in Alzheimer’s disease (AD) pathology. Several studies have demonstrated that nuclear factor kappa-B (NF-ĸB) can contribute to the effects of estrogen on the development of AD. We investigated whether NF-ĸB affects amyloid-beta (Aβ)-induced memory impairment in an estrogen-lacking condition. In the present study, nine-week-old Institute cancer research (ICR) mice were ovariectomized to block estrogen stimulation. Ten weeks after the ovariectomization, mice were administered with Aβ (300 pmol) via intracerebroventricular (ICV) infusion for 2 weeks. Memory impairment, neuroinflammatory protein expression, and amyloidogenic pathways were then measured. Ovariectomized mice demonstrated severe memory impairment, Aβ accumulation, neprilysin downregulation, and activation of NF-ĸB signaling compared to sham-control mice. In vitro experiments demonstrated that β-estradiol (10 μM) inhibited Aβ (1 μM)-induced neuroinflammation in microglial BV-2 cells and prevented Aβ-induced cell death in primary cultured neuronal cells. As in in vivo experiments, NF-ĸB activation was significantly upregulated in in vitro experiments. Furthermore β-estradiol treatment inhibited NF-ĸB activat...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research