Aging alters lipid mediator biosynthesis from polyunsaturated fatty acids in the brain of senescence-accelerated mice with age-related cognitive dysfunction

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  • Sasaki Hideyuki
    Institute for Health Care Science, Suntory Wellness Ltd. Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences
  • Kaneda Yoshihisa
    Institute for Health Care Science, Suntory Wellness Ltd.
  • Rogi Tomohiro
    Institute for Health Care Science, Suntory Wellness Ltd.
  • Shibata Hiroshi
    Institute for Health Care Science, Suntory Wellness Ltd.
  • Aoyagi Ryohei
    Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University
  • Yamane Tsuyoshi
    Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences
  • Ikeda Kazutaka
    Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences
  • Arita Makoto
    Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences

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<p>This study aimed to clarify whether long-chain polyunsaturated fatty acid (LCPUFA) metabolism in the brain that causes an age-related decline of cognitive function changes with aging. The senescence-accelerated mice-prone 10 (SAMP10) is an animal model used in studies related to aging. Young (two-month-old) mice and aged (nine-month-old) mice were fed control diet for 12 weeks. Age-related changes in lipid mediator profiles in the cortex and hippocampus were assessed by comprehensive lipidomics, using liquid chromatography-tandem mass spectrometry after memory examination. The expression of fatty acid metabolism-related mRNAs was evaluated in the hippocampus. Free arachidonic acid (ARA) levels were extremely high among all detected free fatty acids, being approximately 8-fold higher than those of free DHA in the cortex and hippocampus of both young and aged mice. Level of ARA-derived metabolites was extraordinarily high compared to that of other PUFA-derived metabolites, whereas that of DHA-derived metabolites was very low in the cortex and hippocampus of both mice. Aging decreased ARA-derived metabolites in the hippocampus, regardless of the biosynthetic pathway, such as cyclooxygenase, 5-lipoxygenase, 12/15-lipoxygenase, cytochrome P450, and non-enzymatic autoxidation. DHA-derived metabolites in the hippocampus were also decreased by age. There was no significant difference in mRNA expression of the various enzymes related to metabolite biosynthesis between young and aged mice. The cognitive function of SAMP10 was impaired due to aging. Based on analyzing a board range of LCPUFA-derived metabolites, we propose that age-related decrease in LCPUFA metabolism in the hippocampus may be involved in the impaired cognitive function in SAMP10 mice.</p>

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  • Medical Mass Spectrometry

    Medical Mass Spectrometry 4 (1), 65-75, 2020-06-25

    一般社団法人 日本医用マススペクトル学会

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