The effect of cadmium on Aβ levels in APP/PS1 transgenic mice

Li,Xiaoling; Lv,Yongli; Yu,Song; Zhao,Haihua; Yao,Lijie

doi:10.3892/etm.2012.562

The effect of cadmium on Aβ levels in APP/PS1 transgenic mice

Authors:
- Xiaoling Li
- Yongli Lv
- Song Yu
- Haihua Zhao
- Lijie Yao
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Affiliations: Department of Anatomy, China Medical University, Shenyang 110001, P.R. China, Department of Anatomy, Liaoning University of Traditional Chinese Medicine, Shenyang 110032, P.R. China, Department of Anatomy, Qiqihar Medical University, Qiqihar 161006, P.R. China
Published online on: April 26, 2012 https://doi.org/10.3892/etm.2012.562
Pages: 125-130

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Abstract

Cadmium (Cd), which is a poisonous trace element, has been reported extensively to lead to morphological and biochemical abnormalities of the central nervous system, memory loss and mental retardation. We studied the Alzheimer's disease-related toxicity of Cd in a mouse model [amyloid precursor protein (APP)/ presenilin 1 (PS1) transgenic mice, dual transfection of APP695swe and mutated PS1 genes]. Behavioral changes were detected using the Morris water maze test. The β-amyloid protein (Aβ) levels were determined using immunohistochemistry and ELISA. The free zinc ion concentration in mouse brain was determined using autometallography. The protein expression of α-secretase, soluble APPα (sAPPα) and neutral endopeptidase (NEP) in the mouse cerebral cortex and hippocampus was detected using western blotting. We found that Cd treatment increased the latency and distance of the platform search and reduced the number of platform crossings. The number and size of senile plaques in the brains of Cd-treated mice were significantly increased. The levels of Aβ1-42 and free zinc ions were increased. The expression of ADAM10, sAPPα and NEP protein was reduced. We speculated that Cd reduced the expression of ADAM10, sAPPα and NEP protein, which caused an increase in the levels of Aβ1-42 and free zinc ions and led to the accelerated Aβ deposition found in the experimental animals and their abnormal behavior.

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