期刊
FRONTIERS IN CELLULAR NEUROSCIENCE
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2018.00396
关键词
tacrine(10)-hupyridone; post-operative cognitive dysfunction; brain-derived neurotrophic factor; acetylcholinesterase; choline acetyltransferase
资金
- Applied Research Project on Nonprofit Technology of Zhejiang Province [2016C37110]
- Ningbo Natural Science Foundation [2017A610216]
- National Natural Science Foundation of China [31600402]
- Shenzhen Basic Research Program [JCYJ20160331141459373]
- Guangdong-Hong Kong Technology Cooperation Funding Scheme [GHP/012/16GD]
- Research Grants Council of Hong Kong [15101014]
- LiDakSum Marine Biopharmaceutical Development Fund
- K. C. Wong Magna Fund in Ningbo University
Post-operative cognitive dysfunction (POCD) could cause short-term or long-term cognitive disruption lasting weeks or months after anesthesia and surgery in elderly. However, no effective treatment of POCD is currently available. Previous studies indicated that the enhancement of brain-derived neurotrophic factor (BDNF) expression, and the elevation the cholinergic system, might be effective to prevent POCD. In this study, we have discovered that tacrine(10)-hupyridone (A10E), a novel acetylcholinesterase (AChE) inhibitor derived from tacrine and huperzine A, could prevent surgery-induced short-term and long-term impairments of recognition and spatial cognition, as evidenced by the novel object recognition test and Morris water maze (MWM) tests, in aged mice. Moreover, A10E significantly increased the expression of BDNF and activated the downstream Akt and extracellular regulated kinase (ERK) signaling in the surgery-treated mice. Furthermore, A10E substantially enhanced choline acetyltransferase (ChAT)-positive area and decreased AChE activity, in the hippocampus regions of surgery-treated mice, indicating that A10E could prevent surgery-induced dysfunction of cholinergic system, possibly via increasing the synthesis of acetylcholine and the inhibition of AChE. In conclusion, our results suggested that A10E might prevent POCD via the activation of BDNF pathway and the inhibition of AChE, concurrently, in aged mice. These findings also provided a support that A10E might be developed as a potential drug lead for POCD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据