EFFECTS OF COPPER AND/OR CHOLESTEROL OVERLOAD ON MITOCHONDRIAL FUNCTION IN A RAT MODEL OF INCIPIENT NEURODEGENERATION

ARNAL NATHALIE; CASTILLO OMAR; MARÍA ALANIZ; MARRA CARLOS

International journal of Alzheimer's disease

Hindawi Publishing Corporation

Año: 2013

2090-0252

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 during 2 months. Increased amounts of non-ceruloplasmin-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/phospholipd 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 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.