Research Paper Volume 12, Issue 1 pp 543—570

Activation of α7 nAChR by PNU-282987 improves synaptic and cognitive functions through restoring the expression of synaptic-associated proteins and the CaM-CaMKII-CREB signaling pathway

Xiao-Ling Wang1,2,3, , Yu-Xin Deng1,2,3, , Yu-Mei Gao1,2, , Yang-Ting Dong1,2, , Fan Wang4, , Zhi-Zhong Guan1,2,5, , Wei Hong1,2, , Xiao-Lan Qi1,2, ,

  • 1 Key Laboratory of Endemic and Ethnic Diseases, Guizhou Medical University, Ministry of Education, Guiyang 550004, P.R. China
  • 2 Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang 550004, P.R. China
  • 3 School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550004, P.R. China
  • 4 Department of Neurosurgery, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, P.R. China
  • 5 Department of Pathology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, P. R. China

Received: July 16, 2019       Accepted: December 23, 2019       Published: January 6, 2020
How to Cite

Copyright © 2020 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Ligands of nicotinic acetylcholine receptors (nAChRs) are widely considered as potential therapeutic agents. The present study used primary hippocampus cells and APPswe/PSEN1dE9 double-transgenic mice models to study the possible therapeutic effect and underlying mechanism of the specific activation of α7 nAChR by PNU-282987 in the pathogenesis of Alzheimer’s disease. The results indicated that activation of α7 nAChR attenuated the Aβ-induced cell apoptosis, decreased the deposition of Aβ, increased the expression of synaptic-associated proteins, and maintained synaptic morphology. Furthermore, in the APP/PS1_DT mice model, activation of α7 nAChR attenuated Aβ-induced synaptic loss, reduced the deposition of Aβ in the hippocampus, maintained the integral structure of hippocampus-derived synapse, and activated the calmodulin (CaM)-calmodulin-dependent protein kinase II (CaMKII)-cAMP response element-binding protein signaling pathway by upregulation of its key signaling proteins. In addition, activation of α7 nAChR improved the learning and memory abilities of the APP/PS1_DT mice. Collectively, the activation of α7 nAChR by PNU-282987 attenuated the toxic effect of Aβ in vivo and in vitro, which including reduced deposition of Aβ in the hippocampus, maintained synaptic morphology by partially reversing the expression levels of synaptic-associated proteins, activation of the Ca2+ signaling pathway, and improvement of the cognitive abilities of APP/PS1_DT mice.


AD: Alzheimer’s disease; Aβ: β-amyloid peptide; APP/PS1_DT: amyloid precursor protein/Presenilin 1 double-transgenic mice; AP180: adaptor protein of 180 kDa; BCA: background-corrected absorbance; CaM: Calmodulin; CaMKII: calmodulin-binding protein kinase II; CREB: cAMP responsive element-binding protein; CA1: Cornu ammonis 1; DG: dentategyrus; DEPC: diethypyrocarbonate; DYN1: dynamin 1; DAPI: 4,6-diamidino-2-phenylindole; DMSO: dimethyl sulfoxide; ECL: enhanced chemiluminescence; GFAP: Glial fibrillary acidic protein; HFIP: 1,1,1,3,3,3-hexafluoro-2-propanol; IOD: integral optical density; LTP: long-term potentiation; mRNA: messenger ribonucleic acid; MLA: methyllycaconitine; NFTs: neurofibrillary tangles; nAChR: neuronal nicotinic acetylcholine receptor; IOD: integral optical density; PBS: phosphate buffered solution; PSD95: post synaptic density of 95 kDa; PMSF: phenylmethanesulfonyl fluoride; RT-qPCR: reverse transcription quantitative-polymerase chain reaction; SNAP-25: synaptosomal-associated protein of 25; SYN: synaptophysin; SP: senile plaques; TEM: transmission electron microscopy.