Resveratrol up-regulates AMPA receptor expression via AMP-activated protein kinase-mediated protein translation

Neuropharmacology
Guan WangHeng-Ye Man

Abstract

Resveratrol is a phytoalexin that confers overall health benefits including positive regulation in brain function such as learning and cognition. However, whether and how resveratrol affects synaptic activity remains largely unknown. α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are glutamatergic receptors that mediate the majority of fast excitatory transmission and synaptic plasticity, and thus play a critical role in higher brain functions, including learning and memory. We find that in rat primary neurons, resveratrol can rapidly increase AMPAR protein level, AMPAR synaptic accumulation and the strength of excitatory synaptic transmission. The resveratrol effect on AMPAR protein expression is independent of sirtuin 1 (SIRT1), the conventional downstream target of resveratrol, but rather is mediated by AMP-activated protein kinase (AMPK) and subsequent downstream phosphoinositide 3-kinase (PI3K)/Akt signaling. Application of the AMPK specific activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) mimics the effects of resveratrol on both signaling and AMPAR expression. The resveratrol-induced increase in AMPAR expression results from elevated protein synthesis via regulation of the eu...Continue Reading

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Citations

Oct 28, 2015·Future Medicinal Chemistry·Shanshan Lu, Xuefeng Wang
Aug 16, 2016·Metabolic Brain Disease·Mustapha Shehu MuhammadMohammed Garba Magaji
Dec 14, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Zhi GengXiao-Qing Xiong
Jan 7, 2020·Current Neuropharmacology·Elzbieta RebasLudmila Zylinska
Mar 13, 2020·Neurochemical Research·Yan YanHaibing Yu
Apr 16, 2020·International Journal of Molecular Sciences·Arnab Ghosh, Natalia Shcherbik
May 1, 2021·International Journal of Molecular Sciences·Alex J T YangRebecca E K MacPherson

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