The neuroprotective effects of SIRT1 in mice carrying the APP/PS1 double-transgenic mutation and in SH-SY5Y cells over-expressing human APP670/671 may involve elevated levels of α7 nicotinic acetylcholine receptors

摘要

The aim was to determine whether the neuroprotective effect of SIRT1 in Alzheimer’s disease (AD), due to inhibition of aggregation of the β-amyloid peptide (Aβ), involves activation of α7 nAChR. In present study, four-month-old APP/PS1 mice were administered resveratrol (RSV) or suramin once daily for two months, following which their spatial learning and memory were assessed using the Morris water maze test. Deposits of Aβ in vivo were detected by near-infrared imaging (NIRI) and confocal laser scanning. SH-SY5Y/APP cells were treated with RSV, suramin, U0126 or methyllycaconitine (MLA). Levels of proteins and mRNA were determined by Western blotting and qRT-PCR, respectively. The results show that activation of SIRT1 improved their spatial learning and memory and reduced the production and aggregation of Aβ in the hippocampus and cerebral cortex; whereas inhibition of SIRT1 had the opposite effects. In addition, activation of SIRT1 increased the levels of both α7 nAChR and αAPP in the brains these animals. Finally, activation of SIRT1 elevated the levels of pERK1/2, while inhibition of ERK1/2 counteracted the increase in α7 nAChR caused by RSV. These findings indicate that neuroprotection by SIRT1 may involve increasing levels of α7 nAChR through activation of the MAPK/ERK1/2 signaling pathway.