title: Resveratrol improves learning and memory in normally aged mice through microRNA-CREB pathway.
abstract: Resveratrol (RSV) is a natural compound found in grapes and red wine. It has been well known for its beneficial effects as a dietary supplement in prevention of cardiovascular diseases and cancer. Recently, in vitro studies have reported the neuroprotective role of RSV in neurodegenerative process in Alzheimer's disease (AD). However, in vivo effects of RSV on the decline of brain function accompanying the aging process, especially those on cognitive loss, have not been not investigated. Here we report that, after intraventricular injection of RSV for one week in 8-9 month-old mice, the long-term memory formation and the LTP induction from hippocampus CA1 were improved. The RSV enhancement effects were blocked in SIRT1 mutant mice. Additional experiments suggest that RSV effects are likely to be mediated through reduced expressions of miR-134 and miR-124, which may in turn up-regulate CREB levels to subsequently promote BDNF synthesis. These findings demonstrate a role for RSV in cognition and a microRNA-CREB-BDNF mechanism by which RSV regulates these processes, demonstrating its value as a potential therapeutic target against CNS disorders in aging.
authors.affiliation: Model Animal Research Center of Nanjing University and MOE Key Laboratory of Model Animals for Disease Study, 12 Xuefu Road, Pukou High-Tech Zone, Nanjing 210061, China.
authors.forename: Yong-Na
authors.initials: YN
authors.lastname: Zhao
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yun-Dong
authors.initials: YD
authors.lastname: Dai
authors.forename: Ai-Li
authors.initials: AL
authors.lastname: Xu
authors.forename: Cui
authors.initials: C
authors.lastname: Qi
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Gao
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D035683:MicroRNAs; D013267:Stilbenes; D000077185:Resveratrol