The Journal of Nutritional Biochemistry
Volume 20, Issue 12 , Pages 965-973, December 2009

The protective effect of dietary eicosapentaenoic acid against impairment of spatial cognition learning ability in rats infused with amyloid β(1–40)

  • Michio Hashimoto

      Affiliations

    • Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81 853 20 2110; fax: +81 853 20 2110.
  • ,
  • Shahdat Hossain

      Affiliations

    • Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan
  • ,
  • Yoko Tanabe

      Affiliations

    • Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan
  • ,
  • Akiko Kawashima

      Affiliations

    • Developmental Research, Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., Gotemba, Shizuoka 412-8524, Japan
  • ,
  • Tsuyoshi Harada

      Affiliations

    • Developmental Research, Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., Gotemba, Shizuoka 412-8524, Japan
  • ,
  • Takashi Yano

      Affiliations

    • Developmental Research, Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., Gotemba, Shizuoka 412-8524, Japan
  • ,
  • Kiyoshi Mizuguchi

      Affiliations

    • Developmental Research, Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., Gotemba, Shizuoka 412-8524, Japan
  • ,
  • Osamu Shido

      Affiliations

    • Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan

Received 22 March 2008; received in revised form 20 August 2008; accepted 25 August 2008. published online 07 November 2008.

Abstract 

Background

Amyloid β (Aβ) peptide (1–40) can cause cognitive impairment.

Experimental design

We investigated whether dietary preadministration of eicosapentaenoic acid (EPA) is conducive to cognition learning ability and whether it protects against the impairment of learning ability in rats infused with Aβ peptide (1–40) into the cerebral ventricle.

Results

Dietary EPA administered to rats for 12 weeks before the infusion of Aβ into the rat brain significantly decreased the number of reference memory errors (RMEs) and working memory errors (WMEs), suggesting that chronic administration of EPA improves cognition learning ability in rats. EPA preadministered to the Aβ-infused rats significantly reduced the increase in the number of RMEs and WMEs, with concurrent proportional increases in the levels of corticohippocampal EPA and docosahexaenoic acid (DHA) and in the DHA/arachidonic acid molar ratio. Decrease in oxidative stress in these tissues was evaluated by determining the reactive oxygen species and lipid peroxide levels. cDNA microarray analysis revealed that altered genes included those that control synaptic signal transduction, cell communication, membrane-related vesicular transport functions, and enzymes and several other proteins.

Conclusion

The present study suggests that EPA, by acting as a precursor for DHA, ameliorates learning deficits associated with Alzheimer's disease and that these effects are modulated by the expression of proteins involved in neuronal plasticity.

Keywords: Alzheimer's disease, Hippocampus, Spatial memory, Fatty acid, Rat, Amyloid β

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PII: S0955-2863(08)00200-3

doi:10.1016/j.jnutbio.2008.08.009

The Journal of Nutritional Biochemistry
Volume 20, Issue 12 , Pages 965-973, December 2009