Xu, Jingjing, Huang, Xiaochen, Guo, Yujie, Ma, Xiaojun, Li, Pengfei, Zhou, Shaobo ORCID: 0000-0001-5214-2973 , Zhang, Chi, Chen, Rui, Van Halm‐Lutterodt, Nicholas and Yuan, Linhong ORCID: 0000-0001-5169-2527 (2022) 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. Neuropathology and Applied Neurobiology, 49 (1):e12855. ISSN 0305-1846 (Print), 1365-2990 (Online) (doi:https://doi.org/10.1111/nan.12855)

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	dietary docosahexaenoic acid, cerebral lipids, fatty acid transporter expression, soluble beta-amyloid
Subjects:	Q Science > Q Science (General)
Faculty / School / Research Centre / Research Group:	Faculty of Education, Health & Human Sciences Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	20 Oct 2023 01:38
URI:	http://gala.gre.ac.uk/id/eprint/38347

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