Alpha-tocopherol quinine ameliorates spatial memory deficits by reducing beta-amyloid oligomers, neuroinflammation and oxidative stress in transgenic mice with Alzheimer's disease

Shao-Wei Wang; Shi-Gao Yang; Wen Liu; Yang-Xin Zhang; Peng-Xin Xu; Teng Wang; Tie-Jun Ling; Rui-Tian Liu

doi:10.1016/j.bbr.2015.09.003

Alpha-tocopherol quinine ameliorates spatial memory deficits by reducing beta-amyloid oligomers, neuroinflammation and oxidative stress in transgenic mice with Alzheimer's disease

Behav Brain Res. 2016 Jan 1:296:109-117. doi: 10.1016/j.bbr.2015.09.003. Epub 2015 Sep 7.

Authors

Shao-Wei Wang¹, Shi-Gao Yang¹, Wen Liu², Yang-Xin Zhang², Peng-Xin Xu³, Teng Wang², Tie-Jun Ling⁴, Rui-Tian Liu⁵

Affiliations

¹ National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
² National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; School of Life Science, Anhui Agricultural University, Hefei 230036, China.
³ National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; School of Life Science, Ningxia University, Yinchuan 750021, China.
⁴ State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei 230036, China. Electronic address: lingtj@ahau.edu.cn.
⁵ National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: rtliu@ipe.ac.cn.

PMID: 26358659
DOI: 10.1016/j.bbr.2015.09.003

Abstract

The pathologies of Alzheimer's disease (AD) is associated with soluble beta-amyloid (Aβ) oligomers, neuroinflammation and oxidative stress. Decreasing the levels of Aβ oligomer, glial activation and oxidative stress are potential therapeutic approaches for AD treatment. We previously found alpha-tocopherol quinine (α-TQ) inhibited Aβ aggregation and cytotoxicity, decreased the release of inflammatory cytokines and reactive oxygen species (ROS) in vitro. However, whether α-TQ ameliorates memory deficits and other neuropathologies in mice or patients with AD remains unknown. In this study, we reported that orally administered α-TQ ameliorated memory impairment in APPswe/PS1dE9 transgenic mice, decreased oxidative stress and the levels of Aβ oligomer in the brains of mice, prevented the production of inducible nitric oxide synthase and inflammatory mediators, such as interleukin-6 and interleukin-1β, and inhibited microglial activation by inhibiting NF-κB signaling pathway. These findings suggest that α-TQ has potential therapeutic value for AD treatment.

Keywords: Alzheimer’s disease; Beta-amyloid oligomer; NF-κB signaling; Neuroinflammation; Oxidative stress; RRR-α-tocopherol quinine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / drug therapy*
Amyloid beta-Peptides
Animals
Antioxidants / administration & dosage
Antioxidants / pharmacology*
Behavior, Animal / drug effects
Brain / drug effects*
Disease Models, Animal
Inflammation / drug therapy*
Interleukins / metabolism
Memory Disorders / drug therapy*
Mice
Mice, Transgenic
Microglia / drug effects
NF-kappa B / drug effects*
Oxidative Stress / drug effects*
Signal Transduction / drug effects
Spatial Memory / drug effects*
Vitamin E / administration & dosage
Vitamin E / analogs & derivatives*
Vitamin E / pharmacology

Substances

Amyloid beta-Peptides
Antioxidants
Interleukins
NF-kappa B
Vitamin E
tocopherylquinone