Estrogen deficiency exacerbates Aβ-induced memory impairment through enhancement of neuroinflammation, amyloidogenesis and NF-ĸB activation in ovariectomized mice

Brain, Behavior, and Immunity
Jaesuk YunJin Tae Hong

Abstract

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 activation in bot...Continue Reading

Citations

Jul 10, 2019·Journal of Parkinson's Disease·Silvia CerriFabio Blandini
Jun 10, 2020·The Journal of Pharmacology and Experimental Therapeutics·Maricedes Acosta-Martinez
Mar 27, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yongming PanFuliang Hu
May 21, 2020·Frontiers in Aging Neuroscience·Amy ChristensenChristian J Pike
Jul 11, 2020·International Journal of Molecular Sciences·Yvette Akwa
Jan 6, 2021·Journal of Neurology·Megan C BakebergRyan S Anderton
Aug 19, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shu-Qi DongLi-Tao Yi

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