title: Toxicity of cuprizone a Cu(2+) chelating agent on isolated mouse brain mitochondria: a justification for demyelination and subsequent behavioral dysfunction.
abstract: Multiple Sclerosis (MS) is a complex disease with an unknown etiology and no effective cure, despite decades of extensive research that led to the development of several partially effective treatments. In this study we aimed to investigate brain mitochondrial dysfunction in demyelination induced by cuprizone in mice. Cuprizone was used for induction of demyelination in mice through a diet containing 0.2% w/w cuprizone for 5 weeks. Behavioral tests for proving of MS was performed and then mitochondria from brain of animals were isolated and afterwards parameters of mitochondrial dysfunction examined. Results of mitochondrial dysfunction parameters such as mitochondrial swelling, production ROS, collapse of the membrane potential showed that isolated mitochondria from cuprizone treated mice have been damaged compared to those of untreated control mice. It is likely that demyelination induced mitochondrial damage led to increased mitochondrial ROS formation and progression of oxidative damages in neurons. It is suggested that cuprizone which is a Cu(2+) chelating agent causes impairment of electron transport chain (complex IV) and antioxidant system (SOD) in mitochondria leading to decreased ATP production and increased ROS formation.
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran ;
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Faizi
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran ;|b Department of Pharmacology and Toxicology , School of Pharmacy, Ardabil University of Medical Science , Ardabil , Iran ;|c Students Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Salimi
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran ;|c Students Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Enayatolla
authors.initials: E
authors.lastname: Seydi
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran ;|c Students Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Naserzadeh
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran ;
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kouhnavard
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran ;
authors.forename: Atena
authors.initials: A
authors.lastname: Rahimi
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran ;
authors.forename: Jalal
authors.initials: J
authors.lastname: Pourahmad
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002614:Chelating Agents / Q000633:toxicity*; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D005260:Female; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008933:Mitochondrial Swelling / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D045442:Rotarod Performance Test
chemical_list: D002614:Chelating Agents; D017382:Reactive Oxygen Species; D003471:Cuprizone
keywords: Animal model; cuprizone; demyelination; mitochondrial dysfunction