Dietary Cholesterol and Estrogen Administration Elevate Brain Apolipoprotein E in Mice by Different Mechanisms

Abstract

Background: Apolipoprotein (apo) E plays an important role in the whole body cholesterol homeostasis. Recent studies suggest that apoE may also be involved in the local cholesterol transport in the brain, and may influence the pathogenesis of Alzheimer's disease (AD) by interacting with the β-amyloid protein and brain lipoprotein receptors. Purpose: To test the hypothesis that dietary and hormonal interventions, known to regulate hepatic apoE expression, may also regulate brain apoE and thereby influence local cholesterol transport. Methods: Groups of male C57BL mice were fed either regular rodent chow or high fat and high cholesterol (HF) enriched diet for three weeks. In a separate study, groups of male mice were administered pharmacological doses of 17-β estradiol for 5 consecutive days and sacrificed on the sixth day. ApoE mRNA of liver and brain tissues were quantitated by Northern blotting as well as by RNase protection assay. Synthesis of ApoE protein was also quantified. Results: ApoE mRNA and apoE synthesis was increased in liver and brain following HF feeding. Estradiol administration increased liver apoE synthesis without affecting apoE mRNA. Interestingly, estradiol administration also increased brain apoE synthesis, but without altering brain apoE mRNA. Conclusion: These studies suggest that dietary cholesterol and estrogen administrations elevate brain apoE by different mechanisms. doi: 10.5214/ans.0972.7531.2008.150401 Competing interests: None. Source of Funding: None Received Date: 18 Aug 2008 Revised Date: 12 Sept 2008 Accepted Date: 27 Sept 2008