Tocotrienol improves learning and memory deficit of aged rats

Nozomi Kaneai, Kazumi Sumitani, Koji Fukui, Taisuke Koike, Hirokatsu Takatsu, Shiro Urano

Research output: Contribution to journalArticle

8 Citations (Scopus)


To define whether tocotrienol (T-3) improves cognitive deficit during aging, effect of T-3 on learning and memory functions of aged rats was assessed. It was found that T-3 markedly counteracts the decline in learning and memory function in aged rats. Quantitative analysis of T-3 content in the rat brain showed that the aged rats fed T-3 mixture-supplemented diet revealed the transport of α- and γ-T-3 to the brain. In contrast, normal young rats fed the same diet did not exhibit brain localization. Furthermore, the T-3 inhibited age-related decreases in the expression of certain blood brain barrier (BBB) proteins, including caludin-5, occludin and junctional adhesion molecule (JAM). It was found that the activation of the cellular proto-oncogene c-Src and extracellular signal-regulated protein kinase (ERK), in the mitogen-activated protein kinase (MAPK) cell signaling pathway for neuronal cell death, was markedly inhibited by T-3. These results may reveal that aging induces partial BBB disruption caused by oxidative stress, thereby enabling the transport of T-3 through the BBB to the central nervous system, whereupon neuronal protection may be mediated by inhibition of c-Src and/or ERK activation, resulting in an improvement in age-related cognitive deficits.

Original languageEnglish
Pages (from-to)114-121
Number of pages8
JournalJournal of Clinical Biochemistry and Nutrition
Issue number2
Publication statusPublished - 2016 Mar 1


  • Aging
  • BBB
  • c-Src
  • Cognitive deficit
  • Tocotrienol

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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  • Cite this

    Kaneai, N., Sumitani, K., Fukui, K., Koike, T., Takatsu, H., & Urano, S. (2016). Tocotrienol improves learning and memory deficit of aged rats. Journal of Clinical Biochemistry and Nutrition, 58(2), 114-121.