Increased β-amyloid deposition in Tg-SWDI transgenic mouse brain following in vivo lead exposure

被引:52
|
作者
Gu, Huiying [2 ]
Robison, Gregory [1 ]
Hong, Lan
Barrea, Raul [3 ]
Wei, Xing [2 ]
Farlow, Martin R. [2 ]
Pushkar, Yulia N. [1 ]
Du, Yansheng [2 ]
Zheng, Wei [1 ]
机构
[1] Purdue Univ, Sch Hlth Sci, Dept Phys, W Lafayette, IN 47907 USA
[2] Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN 46202 USA
[3] IIT, Dept Biol Chem & Phys Sci, Ctr Synchrotron Radiat Res & Instrumentat, Chicago, IL 60616 USA
关键词
Lead (Pb); Beta-amyloid or A beta; Amyloid plaques; Tg-SWDI mouse; Fibril formation; X-ray fluorescence or XRF; Hippocampus; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; FIBRIL FORMATION; MICE; NEURODEGENERATION; ACCUMULATION; SPECTROSCOPY; CHILDHOOD; RECEPTOR; PLAQUES;
D O I
10.1016/j.toxlet.2012.07.002
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Previous studies in humans and animals have suggested a possible association between lead (Pb) exposure and the etiology of Alzheimer's disease (AD). Animals acutely exposed to Pb display an over-expressed amyloid precursor protein (APP) and the ensuing accumulation of beta-amyloid (A beta) in brain extracellular spaces. This study was designed to examine whether in vivo Pb exposure increased brain concentrations of A beta, resulting in amyloid plaque deposition in brain tissues. Human Tg-SWDI APP transgenic mice, which genetically over-express amyloid plaques at age of 2-3 months, received oral gavages of 50 mg/kg Pb acetate once daily for 6 weeks: a control group of the same mouse strain received the same molar concentration of Na acetate. ELISA results revealed a significant increase of A beta in the CSF, brain cortex and hippocampus. Immunohistochemistry displayed a detectable increase of amyloid plaques in brains of Pb-exposed animals. Neurobehavioral test using Morris water maze showed an impaired spatial learning ability in Pb-treated mice, but not in C57BL/6 wild type mice with the same age. In vitro studies further uncovered that Pb facilitated A beta fibril formation. Moreover, the synchrotron X-ray fluorescent studies demonstrated a high level of Pb present in amyloid plaques in mice exposed to Pb in vivo. Taken together, these data indicate that Pb exposure with ensuing elevated A beta level in mouse brains appears to be associated with the amyloid plaques formation. Pb apparently facilitates A beta fibril formation and participates in deposition of amyloid plaques. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:211 / 219
页数:9
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