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Methylmercury Increases and Eicosapentaenoic Acid Decreases the Relative Amounts of Arachidonic Acid-Containing Phospholipids in Mouse Brain

  • Original Article
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Lipids

Abstract

The membrane phospholipid composition in mammalian brain can be modified either by nutrients such as dietary fatty acids, or by certain toxic substances such as methylmercury (MeHg), leading to various biological and toxic effects. The present study evaluated the effects of eicosapentaenoic acid (EPA) and MeHg on the composition of the two most abundant membrane phospholipid classes, i.e., phosphatidylcholines (PtdCho) and phosphatidylethanolamines (PtdEtn), in mouse brain by using a two-level factorial design. The intact membrane PtdCho and PtdEtn species were analyzed by liquid chromatography–mass spectrometry. The effects of EPA and MeHg on the PtdCho and PtdEtn composition were evaluated by principal component analysis and ANOVA. The results showed that EPA and MeHg had different effects on the composition of membrane PtdCho and PtdEtn species in brain, where EPA showed strongest impact. EPA led to large reductions in the levels of arachidonic acid (ARA)-containing PtdCho and PtdEtn species in brain, while MeHg tended to elevate the levels of ARA-containing PtdCho and PtdEtn species. EPA also significantly increased the levels of PtdCho and PtdEtn species with n-3 fatty acids. Our results indicate that EPA may to some degree counteract the alterations of the PtdCho and PtdEtn pattern induced by MeHg, and thus alleviate the MeHg neurotoxicity in mouse brain through the inhibition of ARA-derived pro-inflammatory factors. These results may assist in the understanding of the interaction between MeHg, EPA and phospholipids, as well as the risk and benefits of a fish diet.

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Abbreviations

ARA:

Arachidonic acid

CerPCho:

Sphingomyelin

DHA:

Docosahexaenoic acid

EFSA:

European food safety authority

EPA:

Eicosapentaenoic acid

LC–MS:

Liquid chromatography–mass spectrometry

LSSR:

Least squares spectral resolution

LTB4 :

Leukotriene B4

MeHg:

Methylmercury

PCA:

Principal component analysis

PGE2 :

Prostaglandin E2

PLA2 :

Phospholipase A2

PtdCho:

Phosphatidylcholines

PtdEtn:

Phosphatidylethanolamines

PUFAs:

Polyunsaturated fatty acids

ROS:

Reactive oxygen species

TBARS:

Thiobarbituric acid reactive substances

TWI:

Tolerable weekly intake

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Acknowledgments

We thank Dr. Lise Madsen for her constructive advices during experimental design and thank Åse Heltveit for help during the animal trial.

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Authors and Affiliations

  1. Department of Chemistry, University of Bergen, PO Box 7803, 5020, Bergen, Norway

    Ying-Xu Zeng, Svein Are Mjøs & Bjørn Grung

  2. School of Life Sciences, East China Normal University, 200241, Shanghai, China

    Zhen-Yu Du

  3. National Institute of Nutrition and Seafood Research (NIFES), PO Box 2029, Nordnes, 5817, Bergen, Norway

    Zhen-Yu Du & Lisa K. Midtbø

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  1. Ying-Xu Zeng
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  2. Zhen-Yu Du
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  3. Svein Are Mjøs
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Correspondence to Zhen-Yu Du or Svein Are Mjøs.

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This work was financially supported by grants from the Norwegian Research Council to NIFES (Project No. 186908 and 199626).

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Zeng, YX., Du, ZY., Mjøs, S.A. et al. Methylmercury Increases and Eicosapentaenoic Acid Decreases the Relative Amounts of Arachidonic Acid-Containing Phospholipids in Mouse Brain. Lipids 51, 61–73 (2016). https://doi.org/10.1007/s11745-015-4087-8

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