Molecular Neurobiology

, Volume 55, Issue 12, pp 9204–9219 | Cite as

Dietary Vitamin E Status Dictates Oxidative Stress Outcomes by Modulating Effects of Fish Oil Supplementation in Alzheimer Disease Model APPswe/PS1dE9 Mice

  • Shengqi Dong
  • Xiaochen Huang
  • Jie Zhen
  • Nicholas Van Halm-Lutterodt
  • JiaJia Wang
  • Cui Zhou
  • Linhong Yuan


Quite a number of studies have examined the effects of fish oil supplementation on cognitive performance in different transgenic animal models of Alzheimer’s disease (AD). However, inconsistent and controversial outcomes have been derived from these experiments. In order to investigate whether the beneficial effect of fish oil supplementation on cognition was dietary VE status associated, fish oil dietary intervention was carried out in transgenic APPswe/PS1dE9 (APP/PS1) mice. Control mice (C57BL/6J mice) were fed a normal control diet. APP/PS1 mice were assigned to a normal control diet group and low VE diet + fish oil supplement, normal VE diet + fish oil supplement, and high VE diet + fish oil supplement groups, respectively. After 7 months of dietary intervention, we found that fish oil supplementation improved behavioral performance, alleviated brain beta-amyloid (Aβ) plaque burden, and attenuated the oxidative stress in APP/PS1 mice by increasing cortical GSH content and total antioxidant capacity, as well as by decreasing MDA level. Fish oil treatment increased cortical n-3 PUFA concentration and decreased n-6/n-3 PUFA ratio in APP/PS1 mice. Fatty acid transporters, Nrf2 and downstream targets involved in cortical and hippocampal antioxidant system were also modulated by fish oil-supplemented diet. Our data demonstrate that fish oil supplementation exerts an enhanced modulatory effect on the antioxidant system and fatty acid concentrations in APP/PS1 mice fed on lowly or averagely concentrated level of VE-containing diet than in mice fed with VE-rich diet. The current data do support previous findings that already dictate the beneficial effect of n-3 PUFAs on cognitive function. Moreover, the cognition promoting effects of n-3 PUFAs may be dietary VE status related.


N-3 polyunsaturated fatty acids Docosahexaenoic acid (DHA) Vitamin E Cognition 


Authors’ Contributions

Linhong Yuan designed the study; Shengqi Dong, Xiaochen Huang, and Jie Zhen carried out the lab work; Linhong Yuan and Nicholas Van Halm-Lutterodt contributed to the data interpretation and drafting of the manuscript; and Cui Zhou and Jiajia Wang performed the statistical analysis.

Funding Information

This study was supported by grants from the National Natural Science Foundation of China (No.81673148) and the 2015 Chinese Nutrition Society (CNS) Nutrition Research Foundation-DSM Research Fund (No. CNS2015070B).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

12035_2018_1060_MOESM1_ESM.docx (16 kb)
ESM 1 (DOCX 16 kb)
12035_2018_1060_MOESM2_ESM.docx (17 kb)
ESM 2 (DOCX 16 kb)


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Authors and Affiliations

  1. 1.School of Public HealthCapital Medical UniversityBeijingPeople’s Republic of China
  2. 2.Department of Orthopaedics and Neurosurgery, Keck Medical Center of USCUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.Department of Neurosurgery, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina
  4. 4.Center for Disease Control and PreventionBeijingPeople’s Republic of China

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