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

• Published in: Behavioural brain research 2016-01, Vol.296, p.109-117
• Main Authors: Wang, Shao-wei, Yang, Shi-gao, Liu, Wen, Zhang, Yang-xin, Xu, Peng-xin, Wang, Teng, Ling, Tie-jun, Liu, Rui-tian
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer’s disease; Amyloid beta-Peptides; Animals; Antioxidants - administration & dosage; Antioxidants - pharmacology; Behavior, Animal - drug effects; Beta-amyloid oligomer; Brain - drug effects; Disease Models, Animal; Inflammation - drug therapy; Interleukins - metabolism; Memory Disorders - drug therapy; Mice; Mice, Transgenic; Microglia - drug effects; Neuroinflammation; NF-kappa B - drug effects; NF-κB signaling; Oxidative stress; Oxidative Stress - drug effects; RRR-α-tocopherol quinine; Signal Transduction - drug effects; Spatial Memory - drug effects; Vitamin E - administration & dosage; Vitamin E - analogs & derivatives; Vitamin E - pharmacology
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2015.09.003

•Alpha-tocopherol quinine ameliorates spatial memory deficits in AD transgenic mice.•Alpha-tocopherol quinine decreases Aβ oligomer levels in the brain of AD transgenic mice.•Alpha-tocopherol quinine inhibits microglia activation by inhibiting NF-κB signaling pathway.•Alpha-tocopherol quinine reduces cytokine production and oxidative stress in AD mice.•Alpha-tocopherol quinine has potential therapeutic value for AD treatment. 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.