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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.
Metallomics. 2017 07 19; 9(7):969-980.M

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.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran. msharifzadeh@tums.ac.ir.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28644490

Citation

Behzadfar, Ladan, et al. "Potentiating Role of Copper On Spatial Memory Deficit Induced By Beta Amyloid and Evaluation of Mitochondrial Function Markers in the Hippocampus of Rats." Metallomics : Integrated Biometal Science, vol. 9, no. 7, 2017, pp. 969-980.
Behzadfar L, Abdollahi M, Sabzevari O, et al. Potentiating role of copper on spatial memory deficit induced by beta amyloid and evaluation of mitochondrial function markers in the hippocampus of rats. Metallomics. 2017;9(7):969-980.
Behzadfar, L., Abdollahi, M., Sabzevari, O., Hosseini, R., Salimi, A., Naserzadeh, P., Sharifzadeh, M., & Pourahmad, J. (2017). Potentiating role of copper on spatial memory deficit induced by beta amyloid and evaluation of mitochondrial function markers in the hippocampus of rats. Metallomics : Integrated Biometal Science, 9(7), 969-980. https://doi.org/10.1039/c7mt00075h
Behzadfar L, et al. Potentiating Role of Copper On Spatial Memory Deficit Induced By Beta Amyloid and Evaluation of Mitochondrial Function Markers in the Hippocampus of Rats. Metallomics. 2017 07 19;9(7):969-980. PubMed PMID: 28644490.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potentiating role of copper on spatial memory deficit induced by beta amyloid and evaluation of mitochondrial function markers in the hippocampus of rats. AU - Behzadfar,Ladan, AU - Abdollahi,Mohammad, AU - Sabzevari,Omid, AU - Hosseini,Rohollah, AU - Salimi,Ahmad, AU - Naserzadeh,Parvaneh, AU - Sharifzadeh,Mohammad, AU - Pourahmad,Jalal, PY - 2017/6/24/pubmed PY - 2018/5/16/medline PY - 2017/6/24/entrez SP - 969 EP - 980 JF - Metallomics : integrated biometal science JO - Metallomics VL - 9 IS - 7 N2 - 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. SN - 1756-591X UR - https://www.unboundmedicine.com/medline/citation/28644490/Potentiating_role_of_copper_on_spatial_memory_deficit_induced_by_beta_amyloid_and_evaluation_of_mitochondrial_function_markers_in_the_hippocampus_of_rats_ L2 - https://doi.org/10.1039/c7mt00075h DB - PRIME DP - Unbound Medicine ER -