title: Tocotrienol improves learning and memory deficit of aged rats.
abstract: 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.
authors.affiliation: Life Support Technology Research Center, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama-shi, Saitama 337-8570 Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Kaneai
authors.affiliation: Department of Bioscience and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama-shi, Saitama 337-8570 Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Sumitani
authors.affiliation: Department of Bioscience and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama-shi, Saitama 337-8570 Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fukui
authors.affiliation: Eisai Food & Chemical Co., LTD., 2-13-10 Nihonbashi, Chuo-ku, Tokyo 103-0027 Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Koike
authors.affiliation: School of Creative Science and Engineering, Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555 Japan.
authors.forename: Hirokatsu
authors.initials: H
authors.lastname: Takatsu
authors.affiliation: Life Support Technology Research Center, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama-shi, Saitama 337-8570 Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Urano
keywords: BBB; aging; c-Src; cognitive deficit; tocotrienol