Dietary Vitamin E Status Dictates Oxidative Stress Outcomes by Modulating Effects of Fish Oil Supplementation in Alzheimer Disease Model APPswe/PS1dE9 Mice
- 395 Downloads
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.
KeywordsN-3 polyunsaturated fatty acids Docosahexaenoic acid (DHA) Vitamin E Cognition
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.
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.
- 2.Gillette Guyonnet S, Abellan Van Kan G, Andrieu S, Barberger Gateau P, Berr C, Bonnefoy M, Dartigues JF, de Groot L et al (2007) IANA task force on nutrition and cognitive decline with aging. J Nutr Health Aging 11:132–152Google Scholar
- 9.Oksman M, Iivonen H, Hogyes E, Amtul Z, Penke B, Leenders I, Broersen L, Lutjohann D et al (2006) Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloidaccumulation in APP/PS1 transgenic mice. Neurobiol Dis 23:563–572CrossRefGoogle Scholar
- 11.Lim W, Gammack J, Van Niekerk J, Dangour A (2006) Omega 3 fatty acid for the prevention of dementia. Cochrane Database Syst Rev. CD005379Google Scholar
- 12.Malouf R, Areosa Sastre A. (2003) Vitamin B12 for cognition.Cochrane Database Syst Rev, CD004326Google Scholar
- 13.Isaac MG, Quinn R, Tabet N(2008) Vitamin E for Alzheimer’sdisease and mild cognitive impairment. Cochrane Database Syst Rev. CD002854Google Scholar
- 19.Lebold KM, Kirkwood JS, Taylor AW, Choi J, Barton CL, Miller GW, La Du J, Jump DB et al (2014) Novel liquid chromatography-mass spectrometry method shows that vitamin E deficiency depletes arachidonic and docosahexaenoic acids in zebrafish (Danio rerio) embryos. Redox Biol 2:105–113CrossRefGoogle Scholar
- 28.Connor WE, Neuringer M, Lin DS (1990) Dietary effects on brain fatty acid composition: the reversibility of n 3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys. J Lipid Res 31:237–247Google Scholar
- 38.Isaac MG, Quinn R, Tabet N (2008) Vitamin E for Alzheimer’s disease and mild cognitive impairment. Cochrane Database Syst Rev 3:CD002854Google Scholar
- 40.Cervantes B, Ulatowski LM (2017) Vitamin E and Alzheimer’s disease—is it time for personalized medicine? Antioxidants (Basel) 6(3)Google Scholar
- 46.Mandal PK, Tripathi M, Sugunan S (2012) Brain oxidative stress: detection and map-ping of anti-oxidant marker ‘glutathione’ in different brain regions of healthy male/female, MCI and Alzheimer patients using non-invasive magnetic resonance spectroscopy. Biochem Biophys Res Commun 417:43–48CrossRefGoogle Scholar
- 50.Zhu H, Fan C, Xu F, Tian C, Zhang F, Qi K (2010) Dietary fish oil n-3 polyunsaturated fatty acids and alpha-linolenic acid differently affect brain accretion of docosahexaenoic acid and expression of desaturases and sterol regulatory element-binding protein 1 in mice. J Nutr Biochem 21:954–960CrossRefGoogle Scholar
- 56.Yu S, Levi L, Casadesus G, Kunos G, Noy N (2014) Fatty acid-binding protein5 (FABP5) regulates cognitive function both by decreasing anandamide levels and by activating the nuclear receptor peroxisome proliferator-activated receptor−/− (PPAR−/−) in the brain. J Biol Chem 289:12748–12758CrossRefGoogle Scholar
- 59.Munteanu A, Taddei M, Tamburini I, Bergamini E, Azzi A, Zingg JM (2006) Antagonistic effects of oxidized low density lipoprotein and alpha-tocopherol on CD36 scavenger receptor expression in monocytes: involvement of protein kinase B and peroxisome proliferator-activated receptor-gamma. J Biol Chem 281:6489–6497CrossRefGoogle Scholar
- 68.Acton SL, Scherer PE, Lodish HF, Krieger M (1994) Expression cloning of SR-BI, a CD36-related class B scavenger receptor. J Biol Chem 269:21003–21009Google Scholar