LiCl attenuates impaired learning and memory of APP/PS1 mice, which in mechanism involves alpha 7 nAChRs and Wnt/beta-catenin pathway

We examined the mechanism by which lithium chloride (LiCl) attenuates the impaired learning capability and memory function of dual-transgenic APP/PS1 mice. Six- or 12-month-old APP/PS1 and wild-type (WT) mice were randomized into four groups, namely WT, WT+Li (100 mg LiCl/kg body weight, gavage once daily), APP/PS1 and APP/PS1+Li. Primary rat hippocampal neurons were exposed to beta-amyloid peptide oligomers (A beta Os), LiCl and/or XAV939 (inhibitor of Wnt/beta-catenin) or transfected with small interfering RNA against the beta-catenin gene. In the cerebral zone of APP/PS1 mice, the level of A beta was increased and those of alpha 7 nicotinic acetylcholine receptors (nAChR), phosphor-GSK3 beta (ser9), beta-catenin and cyclin D1 (protein and/or mRNA levels) reduced. Two-month treatment with LiCl at ages of 4 or 10 months weakened all of these effects. Similar expression variations were observed for these proteins in primary neurons exposed to A beta Os, and these effects were attenuated by LiCl and aggravated by XAV939. Inhibition of beta-catenin expression lowered the level of alpha 7 nAChR protein in these cells. LiCl attenuates the impaired learning capability and memory function of APP/PS1 mice via a mechanism that might involve elevation of the level of alpha 7 nAChR as a result of altered Wnt/beta-catenin signalling.