Copper reduction is related to impairment of cytochrome c oxidase activity in striatum in an animal model of Parkinson's disease

• Published in: Current topics in nutraceuticals research 2012-05, Vol.10 (2), p.87
• Main Authors: Rojas, Patricia, Montes, Sergio, Heras-Romero, Yessica, Montes, Pedro, Rojas, Carolina
• Format: Article
• Language: English
• Subjects: Apoptosis; Brain; Cytochrome c; Cytochrome oxidase; Dopamine; Electron transport; Enzymes; Experiments; Free radicals; Homeostasis; Laboratory animals; Mitochondria; Mitochondrial DNA; Neurodegeneration; Neurophysiology; Neurosciences; Neurotoxicity; Oxidative stress; Parkinson's disease; Pathogenesis; Rodents
• ISSN: 1540-7535; 2641-452X

Copper is an essential transition metal ion for the function of key metabolic enzymes. Copper deficiency produces impairment of mitochondrial function due to a decreased of cytochrome c oxidase activity, this leads to reactive oxygen species production, which in turn triggers mitochondria-mediated apoptotic neurodegeneration. Defects in mitochondrial energy production have been implicated in Parkinson's disease (PD) pathology. Reduction in complex IV (cytochrome c oxidase) activity, the terminal enzyme of the mitochondrial electron transport chain, is copper-dependent and has also been observed in PD. We studied the changes of cytochrome c oxidase activity and copper content in different brain regions in animal model of PD using 1-methyl-4-phenylpyridinium (MPP+). Male Swiss albino mice were treated with saline or MPP+ (18 µg/3 µl, intracerebroventricular). All animals were sacrificed 24 hours after MPP+ administration and different brain regions were removed. Cytochrome c oxidase activity was analyzed using a spectrophotometric technique and copper was determined by atomic absorption analysis. Dopamine levels were measured by HPLC and spontaneous locomotor activity in an activity meter. Cytochrome c oxidase activity was reduced in corpus striatum (27.5%) after MPP+ treatment. However, its activity in cerebellum, midbrain, and frontal cortex was not different from the control group (saline). Copper content decreased only in striatum (56%) and midbrain (31%) after MPP+ administration. Copper administration (CuSO4, 2.5 mg/kg, i.p.) blocked dopaminergic neurotoxicity and displayed a significant reduction (59%) in locomotor activity after MPP+ administration. Our results suggest that copper reduction is related to impairment of cytochrome c oxidase activity in striatum and other parameters in MPP+ neurotoxicity. [PUBLICATION ABSTRACT]