Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice

Lina Wati Durani, Hamizah Shahirah Hamezah, Nor Faeizah Ibrahim, Daijiro Yanagisawa, Muhammad Luqman Nasaruddin, Masaki Mori, Kamalrul Azlan Azizan, Mohd Hanafi Ahmad Damanhuri, Suzana Makpol, Wan Zurinah Wan Ngah, Ikuo Tooyama

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

We have recently shown that the tocotrienol-rich fraction (TRF) of palm oil, a mixture of vitamin E analogs, improves amyloid pathology in vitro and in vivo. However, precise mechanisms remain unknown. In this study, we examined the effects of long-term (10 months) TRF treatment on behavioral impairments and brain metabolites in (15 months old) AβPP/PS1 double transgenic (Tg) Alzheimer's disease (AD) mice. The open field test, Morris water maze, and novel object recognition tasks revealed improved exploratory activity, spatial learning, and recognition memory, respectively, in TRF-treated Tg mice. Brain metabolite profiling of wild-type and Tg mice treated with and without TRF was performed using ultrahigh performance liquid chromatography (UHPLC) coupled to high-resolution accurate mass (HRAM)-orbitrap tandem mass spectrometry (MS/MS). Metabolic pathway analysis found perturbed metabolic pathways that linked to AD. TRF treatment partly ameliorated metabolic perturbations in Tg mouse hippocampus. The mechanism of this pre-emptive activity may occur via modulation of metabolic pathways dependent on Aβ interaction or independent of Aβ interaction.

Original languageEnglish
Pages (from-to)249-267
Number of pages19
JournalJournal of Alzheimer's Disease
Volume64
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Fingerprint

Tocotrienols
Metabolic Networks and Pathways
Transgenic Mice
Alzheimer Disease
Brain
Tandem Mass Spectrometry
Vitamin E
Amyloid
Liquid Chromatography
Hippocampus
palm oil
Pathology
Water

Keywords

  • Alzheimer's disease
  • behavioral impairments
  • metabolomics
  • pre-emptive medicine
  • tocotrienol

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Durani, L. W., Hamezah, H. S., Ibrahim, N. F., Yanagisawa, D., Nasaruddin, M. L., Mori, M., ... Tooyama, I. (2018). Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice. Journal of Alzheimer's Disease, 64(1), 249-267. https://doi.org/10.3233/JAD-170880

Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice. / Durani, Lina Wati; Hamezah, Hamizah Shahirah; Ibrahim, Nor Faeizah; Yanagisawa, Daijiro; Nasaruddin, Muhammad Luqman; Mori, Masaki; Azizan, Kamalrul Azlan; Ahmad Damanhuri, Mohd Hanafi; Makpol, Suzana; Wan Ngah, Wan Zurinah; Tooyama, Ikuo.

In: Journal of Alzheimer's Disease, Vol. 64, No. 1, 01.01.2018, p. 249-267.

Research output: Contribution to journalArticle

Durani, Lina Wati ; Hamezah, Hamizah Shahirah ; Ibrahim, Nor Faeizah ; Yanagisawa, Daijiro ; Nasaruddin, Muhammad Luqman ; Mori, Masaki ; Azizan, Kamalrul Azlan ; Ahmad Damanhuri, Mohd Hanafi ; Makpol, Suzana ; Wan Ngah, Wan Zurinah ; Tooyama, Ikuo. / Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice. In: Journal of Alzheimer's Disease. 2018 ; Vol. 64, No. 1. pp. 249-267.
@article{82f609a972c345688660c7870146f8a0,
title = "Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice",
abstract = "We have recently shown that the tocotrienol-rich fraction (TRF) of palm oil, a mixture of vitamin E analogs, improves amyloid pathology in vitro and in vivo. However, precise mechanisms remain unknown. In this study, we examined the effects of long-term (10 months) TRF treatment on behavioral impairments and brain metabolites in (15 months old) AβPP/PS1 double transgenic (Tg) Alzheimer's disease (AD) mice. The open field test, Morris water maze, and novel object recognition tasks revealed improved exploratory activity, spatial learning, and recognition memory, respectively, in TRF-treated Tg mice. Brain metabolite profiling of wild-type and Tg mice treated with and without TRF was performed using ultrahigh performance liquid chromatography (UHPLC) coupled to high-resolution accurate mass (HRAM)-orbitrap tandem mass spectrometry (MS/MS). Metabolic pathway analysis found perturbed metabolic pathways that linked to AD. TRF treatment partly ameliorated metabolic perturbations in Tg mouse hippocampus. The mechanism of this pre-emptive activity may occur via modulation of metabolic pathways dependent on Aβ interaction or independent of Aβ interaction.",
keywords = "Alzheimer's disease, behavioral impairments, metabolomics, pre-emptive medicine, tocotrienol",
author = "Durani, {Lina Wati} and Hamezah, {Hamizah Shahirah} and Ibrahim, {Nor Faeizah} and Daijiro Yanagisawa and Nasaruddin, {Muhammad Luqman} and Masaki Mori and Azizan, {Kamalrul Azlan} and {Ahmad Damanhuri}, {Mohd Hanafi} and Suzana Makpol and {Wan Ngah}, {Wan Zurinah} and Ikuo Tooyama",
year = "2018",
month = "1",
day = "1",
doi = "10.3233/JAD-170880",
language = "English",
volume = "64",
pages = "249--267",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "1",

}

TY - JOUR

T1 - Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice

AU - Durani, Lina Wati

AU - Hamezah, Hamizah Shahirah

AU - Ibrahim, Nor Faeizah

AU - Yanagisawa, Daijiro

AU - Nasaruddin, Muhammad Luqman

AU - Mori, Masaki

AU - Azizan, Kamalrul Azlan

AU - Ahmad Damanhuri, Mohd Hanafi

AU - Makpol, Suzana

AU - Wan Ngah, Wan Zurinah

AU - Tooyama, Ikuo

PY - 2018/1/1

Y1 - 2018/1/1

N2 - We have recently shown that the tocotrienol-rich fraction (TRF) of palm oil, a mixture of vitamin E analogs, improves amyloid pathology in vitro and in vivo. However, precise mechanisms remain unknown. In this study, we examined the effects of long-term (10 months) TRF treatment on behavioral impairments and brain metabolites in (15 months old) AβPP/PS1 double transgenic (Tg) Alzheimer's disease (AD) mice. The open field test, Morris water maze, and novel object recognition tasks revealed improved exploratory activity, spatial learning, and recognition memory, respectively, in TRF-treated Tg mice. Brain metabolite profiling of wild-type and Tg mice treated with and without TRF was performed using ultrahigh performance liquid chromatography (UHPLC) coupled to high-resolution accurate mass (HRAM)-orbitrap tandem mass spectrometry (MS/MS). Metabolic pathway analysis found perturbed metabolic pathways that linked to AD. TRF treatment partly ameliorated metabolic perturbations in Tg mouse hippocampus. The mechanism of this pre-emptive activity may occur via modulation of metabolic pathways dependent on Aβ interaction or independent of Aβ interaction.

AB - We have recently shown that the tocotrienol-rich fraction (TRF) of palm oil, a mixture of vitamin E analogs, improves amyloid pathology in vitro and in vivo. However, precise mechanisms remain unknown. In this study, we examined the effects of long-term (10 months) TRF treatment on behavioral impairments and brain metabolites in (15 months old) AβPP/PS1 double transgenic (Tg) Alzheimer's disease (AD) mice. The open field test, Morris water maze, and novel object recognition tasks revealed improved exploratory activity, spatial learning, and recognition memory, respectively, in TRF-treated Tg mice. Brain metabolite profiling of wild-type and Tg mice treated with and without TRF was performed using ultrahigh performance liquid chromatography (UHPLC) coupled to high-resolution accurate mass (HRAM)-orbitrap tandem mass spectrometry (MS/MS). Metabolic pathway analysis found perturbed metabolic pathways that linked to AD. TRF treatment partly ameliorated metabolic perturbations in Tg mouse hippocampus. The mechanism of this pre-emptive activity may occur via modulation of metabolic pathways dependent on Aβ interaction or independent of Aβ interaction.

KW - Alzheimer's disease

KW - behavioral impairments

KW - metabolomics

KW - pre-emptive medicine

KW - tocotrienol

UR - http://www.scopus.com/inward/record.url?scp=85048536889&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048536889&partnerID=8YFLogxK

U2 - 10.3233/JAD-170880

DO - 10.3233/JAD-170880

M3 - Article

VL - 64

SP - 249

EP - 267

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 1

ER -