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Title: Tacrine(10)-hupyridone prevents post-operative cognitive dysfunction via the activation of BDNF pathway and the inhibition of AChE in aged mice
Authors: Chen, HX
Wu, X
Gu, XM
Zhou, YY
Ye, LY
Zhang, K
Pan, HB
Wang, JL
Wei, H
Zhu, BB
Naman, CB
Mak, S 
Carlier, PR
Cui, W
Han, YF 
Keywords: Tacrine(10)-hupyridone
Post-operative cognitive dysfunction
Brain-derived neurotrophic factor
Choline acetyltransferase
Issue Date: 2018
Publisher: Frontiers Research Foundation
Source: Frontiers in cellular neuroscience, Nov. 2018, v. 12, 396, p. 1-11 How to cite?
Journal: Frontiers in cellular neuroscience 
Abstract: 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.
EISSN: 1662-5102
DOI: 10.3389/fncel.2018.00396
Rights: Copyright © 2018 Chen, Wu, Gu, Zhou, Ye, Zhang, Pan, Wang, Wei, Zhu, Naman, Mak, Carlier, Cui and Han. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)( The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The following publication Chen, H.X., Wu, X., Gu, X.M., Zhou, Y.Y., Ye, L.Y., Zhang, K., ... & Han, Y.F. (2018). Tacrine(10)-hupyridone prevents post-operative cognitive dysfunction via the activation of BDNF pathway and the inhibition of AChE in aged mice. Frontiers in cellular neuroscience, 12, 396, 1-11 is available at
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