Neurodegeneration associated to copper and cholesterol administration in Wistar rats.

ARNAL, NATHALIE; CARLOS A. MARRA

Córdoba

Congreso; XXIX Congreso Anual de la Sociedad Argentina de Investigaciones en Neurociencia; 2014

Copper (Cu) and cholesterol (Cho) are associated to neurodegeneration. We have demonstrated that supplementation of Wistar rats for 2 months with Cu (3 ppm-drinking water) associated to Cho (2 %-diet) produced oxidative and inflammatory damages in cortex (CT) and hippocampus (HYP). It also increased AB(1-42)/(1-40) ratio in brain. The aim of this work was to study the effect of CuCho in Wistar rats over time (2 to 6 months) in order to investigate a possible synergistic action during the progression of the neurodegeneration. We measured total and non-ceruloplasmin bound-Cu (NCBC), Cho (free and sterified), markers of oxidative stress (OS), inflammation, programmed cell death (caspase-3 and calpains) in CT and HYP, and the ratio AB(1-42)/(1-40) in plasma and brain. Our results shows a time-dependent increase of NCBC, free and sterified Cho, OS and inflammatory biomarkers in CT and HYP that agree with an increased GSSG/GSH ratio, and decreased VitE levels. Only calpains activity increase after 2 months, whereas caspase-3 activity does it after 4 months. Then, calpains relieve caspase-3. Increases in AB(1-42)/(1-40) ratio was found in CT and HYP after 4 and 6 months. After 2 months, only HYP shows such increase. This ratio increased in plasma in a time-dependent fashion. We conclude that this model could be used to study the mechanisms underlying the neurodegenerative action of CuCho, contributing to find new markers of neurodegenerative risk in susceptible populations.