Open AccessLiCl attenuates impaired learning and memory of APP/PS1 mice, which in mechanism involves α7 nAChRs and Wnt/β‐catenin pathway
Author(s) -
Xiang Jie,
Ran LongYan,
Zeng XiaoXiao,
He WenWen,
Xu Yi,
Cao Kun,
Dong YangTing,
Qi XiaoLan,
Yu WenFeng,
Xiao Yan,
Guan ZhiZhong
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17006
Subject(s) - wnt signaling pathway , chemistry , medicine , endocrinology , hippocampus , catenin , genetically modified mouse , amyloid precursor protein , hippocampal formation , cyclin d1 , morris water navigation task , microbiology and biotechnology , transgene , signal transduction , biology , biochemistry , alzheimer's disease , cell cycle , cell , disease , gene
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 β‐amyloid peptide oligomers (AβOs), LiCl and/or XAV939 (inhibitor of Wnt/β‐catenin) or transfected with small interfering RNA against the β‐catenin gene. In the cerebral zone of APP/PS1 mice, the level of Aβ was increased and those of α7 nicotinic acetylcholine receptors (nAChR), phosphor‐GSK3β (ser9), β‐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 AβOs, and these effects were attenuated by LiCl and aggravated by XAV939. Inhibition of β‐catenin expression lowered the level of α7 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 α7 nAChR as a result of altered Wnt/β‐catenin signalling.