增食欲素
莫里斯水上航行任务
发病机制
食欲素-A
内分泌学
内科学
医学
转基因小鼠
线粒体
分子生物学
神经肽
化学
生物
海马体
细胞生物学
转基因
生物化学
基因
受体
作者
Maoyu Li,Yao Meng,Bingcong Chu,Yang Shen,Xinhong Xue,Chaoyuan Song,Xiangtian Liu,Mao Ding,Xi Cao,Ping Wang,Shunliang Xu,Jianzhong Bi,Zhaohong Xie
标识
DOI:10.1016/j.neulet.2020.134741
摘要
Alzheimer’s disease (AD) is a progressive neurodegenerative disease which is characterized by the accumulation of amyloid-β peptide (Aβ). Orexin-A is a neuropeptide which has been reported to participate in the pathogenesis of AD. Thus, we aimed to investigate the possible mechanism by which Orexin-A acts in AD. APP/PS1 transgenic mice, an animal model of AD, were intracerebroventricularly injected with Orexin-A. Aβ-treated SH-SY5Y cells were used as a cell model of AD and treated with Orexin-A. The Morris water maze test, fluorescence microscopy, enzyme-linked immunosorbent assay (ELISA), electron microscopy, real-time PCR, and other biochemical assays were conducted. The Morris water maze test showed that Orexin-A aggravated cognitive deficit in APP/PS1 mice. Using thioflavine-S staining and ELISA, we found that Orexin-A promoted Aβ accumulation in APP/PS1 mice. By evaluating mitochondrial morphology, cytochrome c oxidase activity, ATP level, mitochondrial DNA copy number, and reactive oxygen species, we found that Orexin-A aggravated mitochondrial impairment in APP/PS1 mice and Aβ-treated SH-SY5Y cells. Our results indicate that Orexin-A exacerbates AD by inducing mitochondrial impairment. This is a new mechanism that explains how Orexin-A participates in the pathogenesis of AD.
科研通智能强力驱动
Strongly Powered by AbleSci AI