Association of copper and cholesterol supplementation with the development of hypercholesterolemic brains

ARNAL, NATHALIE; ASTIZ MARIANA; MONTANARO MAURO; CARLOS A. MARRA

Río de Janeiro

Congreso; 9° World Congress International Brain Research Organization; 2015

IBRO (International Brain Research Organization)

Alzheimer disease (AD) is a progressive neurodegeneration that has no cure and its prevalence increases with time. AD can be classified in familial-AD (associated to specific genes) (5 %) and sporadic-AD (without genetic risk) (95 %). The majority of the patients with sporadic-AD are hypercholesterolemic taking statins to lower cholesterol (Cho) levels. Copper (Cu) overload is also associated to the development of neurodegeneration, and many people are exposed to elevated levels of this metal bythe use of Cu plumbing (Cu in drinking water) and the ingestion of Cu multi-mineral supplements. We have previously demonstrated that supplementation of male Wistar rats for 4 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 Aβ (1-42)/(1-40) ratio in brain. The aim of this work was to study the effects of Cu and Cho supplementation (alone or simultaneously) on Cu and Cho (total, free and sterified) levels in CT and HYP of male wistar rats after 4 months of treatment. In addition, we analyzed the levels of the main regulatory enzyme in the Cho synthesis pathway: 3hydroxy 3 methyl glutaryl-coenzyme A reductase (HMGCoAR) and the levels of the transcription factor involved in the activation of HMGCoAR transcription: SREBP2. Our results demonstrated that in both brain zones Cu levels increased after Cu and Cu + Cho administration. However, total Cho (TCho) always increased (Cu, Cho and Cu + Cho). It is interesting to note that with the ingestion of Cho alone TCho increased at expense of free Cho and when Cu was present TCho also increased at expense of sterified Cho. The levels of HMGCoAR and SREBP2 showed no significant changes within treatments. We conclude that Cho administered in food could be able to enter the brain producing increases of TCho levels, being higher when co-supplemented with Cu by a mechanism not elucidated yet.