title: Effects of Copper and/or Cholesterol Overload on Mitochondrial Function in a Rat Model of Incipient Neurodegeneration.
abstract: Copper (Cu) and cholesterol (Cho) are both associated with neurodegenerative illnesses in humans and animals models. We studied the effect in Wistar rats of oral supplementation with trace amounts of Cu (3 ppm) and/or Cho (2%) in drinking water for 2 months. Increased amounts of nonceruloplasmin-bound Cu were observed in plasma and brain hippocampus together with a higher concentration of ceruloplasmin in plasma, cortex, and hippocampus. Cu, Cho, and the combined treatment Cu + Cho were able to induce a higher Cho/phospholipid ratio in mitochondrial membranes with a simultaneous decrease in glutathione content. The concentration of cardiolipin decreased and that of peroxidation products, conjugated dienes and lipoperoxides, increased. Treatments including Cho produced rigidization in both the outer and inner mitochondrial membranes with a simultaneous increase in permeability. No significant increase in Cyt C leakage to the cytosol was observed except in the case of cortex from rats treated with Cu and Cho nor were there any significant changes in caspase-3 activity and the Bax/Bcl2 ratio. However, the A β (1-42)/(1-40) ratio was higher in cortex and hippocampus. These findings suggest an incipient neurodegenerative process induced by Cu or Cho that might be potentiated by the association of the two supplements.
authors.affiliation: Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CCT La Plata, CONICET-UNLP, Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, 1900 La Plata, Argentina.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Arnal
authors.affiliation: Centro de Investigaciones Cardiovasculares (CIC), CCT-CONICET, 1900 La Plata, Argentina.
authors.forename: Omar
authors.initials: O
authors.lastname: Castillo
authors.affiliation: Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CCT La Plata, CONICET-UNLP, Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, 1900 La Plata, Argentina.
authors.forename: María J T
authors.initials: MJ
authors.lastname: de Alaniz
authors.affiliation: Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CCT La Plata, CONICET-UNLP, Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, 1900 La Plata, Argentina ; INIBIOLP, Cátedra de Bioquímica, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Calles 60 y 120, 1900 La Plata, Argentina.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Marra