文献类型：期刊文献

英文题名：Lead exposure induces Alzheimers's disease (AD)-like pathology and disturbes cholesterol metabolism in the young rat brain

作者：Zhou, Can-Can[1];Gao, Zhen-Yan[1];Wang, Ju[1];Wu, Mei-Qin[1];Hu, Shuang[2];Chen, Fei[2];Liu, Jun-Xia[1];Pan, Hui[1];Yan, Chong-Huai[1]

机构：[1]Shanghai Jiao Tong Univ, MOE Shanghai Key Lab Childrens Environm Hlth, Xinhua Hosp, Sch Med, Shanghai 200092, Peoples R China;[2]East China Univ Sci & Technol, Shanghai 200237, Peoples R China

年份：2018

卷号：296

起止页码：173

外文期刊名：TOXICOLOGY LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000442583400019)】；

基金：This work was supported by the National Basic Research Program of China (973 Program, 2012CB525001) and the National Natural Science Foundation of China (Grant No. 81472993). In addition, Cancan Zhou especially want to thank the support and love from his fiancee Yuqiong He.

语种：英文

外文关键词：Lead; AD-like pathology; Cholesterol metabolism; SREBP2-BACE1 pathway

摘要：Lead exposure has been evidenced as a risk factor for Alzheimer's disease (AD), mainly affecting the ageing. However, the early manifestation and mechanisms of AD-like pathology induced by lead exposure remains to be elucidated. Considering the fact that impaired cholesterol metabolism is associated with many neurodegenerative disorders including AD, in this study we focused on the role of cholesterol metabolism in lead induced premature AD-like pathology. We treated weaning rats with lead at different concentrations for 4 weeks. We found that developmental lead exposure increased amyloid-beta (A ss) accumulation and amyloid plaque deposition in the cortex and hippocampus. Lead exposure increased amyloid precursor protein (APP) expression and activated the sterol regulatory element binding protein 2 (SREBP2)-beta secretase (BACE1) pathway. In addition, we found that lead exposure decreased cholesterol levels by upregulating the expression of liver X receptor-a (LXR-a) and ATP-binding cassette transporter protein family member A1 (ABCA1) and decreasing the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR) and low density lipoprotein receptor (LDLR) in young rat brain tissues. Taken together, our data demonstrated that developmental lead exposure induced early manifestation of AD-like pathology and disturbed cholesterol metabolism in young rat brains.