Discrepant modulating effects of dietary docosahexaenoic acid on cerebral lipids, fatty acid transporter expression and soluble beta‐amyloid levels in ApoE −/− and C57BL/6J mice

Aims The study was designed to explore the role of apolipoprotein E (ApoE) deficiency concomitant with dietary docosahexaenoic acid (DHA) treatment on brain β-amyloid (Aβ) and lipid levels. Method A 5-month dietary DHA intervention was conducted in ApoE-deficient (ApoE−/−) mice and wild-type C57BL/6J (C57 wt) mice. The Morris water maze test was performed to assess the behaviour of the animals. The cortical contents of soluble Aβ1–40 and Aβ1–42 were detected by enzyme-linked immunosorbent assay (ELISA). Cortical fatty acid levels were detected by gas chromatography. Gene and protein expression of molecules associated with cerebral Aβ and lipid metabolism were measured using real-time polymerase chain reaction (PCR), Western blot and histological methods. Results DHA treatment increased the content of cortical DHA and n-3 polyunsaturated fatty acids (n-3 PUFAs) but decreased the ratio of n-6/n-3 PUFAs in ApoE−/− mice; whereas the content of cortical DHA and n-3 PUFAs in C57 wt mice remained unchanged after DHA treatment. Cerebral Fabp5 and Cd36 gene expression were significantly downregulated in DHA-fed C57 wt mice; cerebral Cd36 and Scarb1 gene expression were significantly upregulated, whereas Fabp5 gene expression was downregulated in DHA-fed ApoE−/− mice. In comparison with C57 wt mice, the content of cortical soluble Aβ1–42, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) increased, whereas the level of high-density lipoprotein cholesterol (HDL-C) decreased in ApoE−/− mice. Interestingly, these differences were significantly reversed by DHA dietary treatment. Conclusion DHA intervention has discrepant impacts on cerebral lipids, fatty acid transporter expression and soluble Aβ levels in ApoE−/− and C57 wt mice, suggesting the modifying role of ApoE status on the responses of cerebral lipids and Aβ metabolism to DHA treatment