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

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 alpha7 nAChR by PNU-282987 in the pathogenesis of Alzheimer's disease. The results indicated that activation of alpha7 nAChR attenuated the Abeta-induced cell apoptosis, decreased the deposition of Abeta, increased the expression of synaptic-associated proteins, and maintained synaptic morphology. Furthermore, in the APP/PS1_DT mice model, activation of alpha7 nAChR attenuated Abeta-induced synaptic loss, reduced the deposition of Abeta 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 alpha7 nAChR improved the learning and memory abilities of the APP/PS1_DT mice. Collectively, the activation of alpha7 nAChR by PNU-282987 attenuated the toxic effect of Abeta in vivo and in vitro, which including reduced deposition of Abeta in the hippocampus, maintained synaptic morphology by partially reversing the expression levels of synaptic-associated proteins, activation of the Ca(2+) signaling pathway, and improvement of the cognitive abilities of APP/PS1_DT mice.