Environmental lead exposure aggravates the progression of Alzheimer's disease in mice by targeting on blood brain barrier. (1st February 2020)

• Record Type: Journal Article
• Authors: Wu, Sai; Liu, Huaixiang; Zhao, Heping; Wang, Xiaohui; Chen, Jingli; Xia, Dong; Xiao, Chen; Cheng, Jianding; Zhao, Zhiqiang; He, Yun
• Is Part Of: Toxicology letters. Volume 319(2020)
• Page Start: 138
• Page End: 147
• Publication Date: 2020-02-01
• Subjects: Lead -- Alzheimer's disease -- Blood-brain barrier -- APP/PS1 gene; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2019.11.009
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: The mode of exposure was similar to the pattern of human exposure to lead, including chronic lead exposure from mother mice to their offspring. Lead exposure increased the expression and vascular deposition of Aβ1–42 in the brain of APP/PS1 mice. Lead exposure activated astrocytes and promoted astrocytes' co-location with Aβ1–42 plaque in the brain of APP/PS1 mice. Lead exposure induced abnormal expression of ZO-1 and Claudin-5, and increased the expression of p-tau protein. Lead exposure reduced LRP-1 expression and increased APP and BACE-1 expression. Abstract: Alzheimer's disease (AD) is a neurodegenerative disease that can be induced by heavy metals such as lead. However, there is limited information on the role of blood-brain barrier (BBB) in lead induced AD-like pathology. This study investigates the potential mechanism of lead exposure aggravating the progression of Alzheimer's disease in mice through the BBB. 200 mg/L and 500 mg/L lead acetate were given to C57BL/6J and APP/PS1 mice through drinking water from a week before mating, until the offspring were 7-months-old. 8 female juvenile mice in each group were selected for this investigation. Lead exposure increased blood lead concentration which revealed the internal exposure level, accelerated Aβ1-42 deposition in APP/PS1 mouse cortexes and abnormal change in Zonula Occludin-1 (ZO-1) and Claudin-5 protein. It also increased the expression of p-tau in both the C57BL/6J and APP/PS1 mice, and decreased mRNA and protein expression in low-density lipoprotein receptor (LRP-1). Additionally, it increased the mRNA and protein expression of amyloid beta precursor protein (APP) and beta secretase 1 (BACE-1). The activated astrocytes increased in the brains of APP/PS1 mice, and coalesced around the Aβ1-42 deposition after lead exposure. The main vessels in deutocerebrum were attached with Aβ1-42 deposition. These results offer insight into the mechanism of preventing lead induced AD through cerebrovascular pathways.