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Issue 7, 2017
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Potentiating role of copper on spatial memory deficit induced by beta amyloid and evaluation of mitochondrial function markers in the hippocampus of rats

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Abstract

Mounting evidence suggests that copper, a crucial element in normal brain function, plays an important role in the etiology of Alzheimer's disease, which is known as a neurodegenerative mitochondrial disorder. However, the precise mechanisms of its effects on cognitive and mitochondrial functions through the CNS have not been thoroughly recognized yet. In this study, we aimed to investigate the long-term (3-week) effects of copper sulfate (50, 100 and 200 mg kg−1 day−1) exposure on learning and memory as well as on mitochondrial function in the hippocampus of rats in the presence and absence of beta amyloid (1 μg μl−1 per side) intrahippocampally (IH). After three weeks of copper exposure through drinking water, acquisition and retention of spatial memory were measured by the Morris water maze (MWM) test. Various parameters of mitochondrial function were also evaluated. Our data show that copper damaged the spatial learning and memory and also exacerbated the memory deficit induced by Aβ injection in rats in a dose-dependent manner. Mitochondria isolated from the hippocampus of rats treated with copper showed significant increases in ROS formation, mitochondrial swelling, lipid peroxidation, glutathione oxidation, outer membrane damage, and collapse of MMP, decreased cytochrome c oxidase activity, and finally increased ADP/ATP ratios. Our results indicate that copper overloading in the hippocampus of rats causes mitochondrial dysfunction and subsequent oxidative stress leading to cognitive impairment. This study also reveals that copper can potentiate Aβ deleterious effects on spatial memory and brain mitochondrial function.

Graphical abstract: Potentiating role of copper on spatial memory deficit induced by beta amyloid and evaluation of mitochondrial function markers in the hippocampus of rats

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Publication details

The article was received on 16 Mar 2017, accepted on 03 May 2017 and first published on 03 May 2017


Article type: Paper
DOI: 10.1039/C7MT00075H
Citation: Metallomics, 2017,9, 969-980
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    Potentiating role of copper on spatial memory deficit induced by beta amyloid and evaluation of mitochondrial function markers in the hippocampus of rats

    L. Behzadfar, M. Abdollahi, O. Sabzevari, R. Hosseini, A. Salimi, P. Naserzadeh, M. Sharifzadeh and J. Pourahmad, Metallomics, 2017, 9, 969
    DOI: 10.1039/C7MT00075H

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