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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.

Abstract

Abstract Mounting evidence suggests that copper, a crucial element in normal brain function, played an important role in the etiology of Alzheimer’s disease which is known as a neurodegenerative mitochondrial disorder. But the precise mechanisms of its effects on cognitive and mitochondrial function trough the CNS has not been thoroughly recognized yet. In this study, we aimed to investigate the long-term effects of (3 weeks) copper sulfate (50, 100 and 200 mg/kg/day) exposure on learning and memory as well as on mitochondrial function in the hippocampus of rats in the presence and absence of beta amyloid (1µg/µl 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 showed 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 increase in ROS formation, mitochondrial swelling, lipid peroxidation, glutathione oxidation, outer membrane damage, collapse of MMP, decreased cytochrome c oxidase activity, and finally increased ADP/ATP ratio. Our results indicated that copper overloading in the hippocampus of rats causes mitochondrial dysfunction and subsequent oxidative stress leading to cognitive impairment. This study also revealed that copper can potentiate Aβ deleterious effects on spatial memory and brain mitochondrial function. Keywords: Copper, Beta amyloid, Spatial memory, Mitochondrial function, hippocampus. Abbreviations: MWM, Morris water maze test; Aβ, beta-amyloid peptide 1–42; ROS, reactive oxygen species; MMP, mitochondrial membrane potential; IH, intrahippocampally.

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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, Accepted Manuscript
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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.

    J. Pourahmad, L. behzadfar, M. sharifzadeh, M. Abdollahi, O. sabzevari, R. hosseini and A. Salimi, Metallomics, 2017, Accepted Manuscript , DOI: 10.1039/C7MT00075H

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