Resveratrol and pinostilbene confer neuroprotection against aging-related deficits through an ERK1/2-dependent mechanism |
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| Institution: | 1. Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, United States;2. Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA 15260, United States;3. Center for Translational Research in Neurodegenerative Disease, College of Medicine University of Florida, Gainesville, FL, 32610, United States;4. Department of Pharmacology, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Boulevard, Erie, PA 16509, United States;5. United States Department of Agriculture, Agricultural Research Service, University Avenue, University, MS 386770000;1. Education Ministry Key Laboratory of Integrated Management of Crop Diseases and Pests, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China;2. State Key Laboratory of Rice Biology, China National Rice Research Institute, Hangzhou 310006, China;1. Regional Blood Center of Ribeirão Preto, Ribeirão Preto School of Medicine, University of São Paulo, Brazil;2. Department of Biomechanics, Medicine and Rehabilitation of the Locomotor System, Ribeirão Preto Medical School, University of São Paulo, Brazil;3. Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;4. Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo, Brazil |
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| Abstract: | Age-related declines in motor function may be due, in part, to an increase in oxidative stress in the aging brain leading to dopamine (DA) neuronal cell death. In this study, we examined the neuroprotective effects of natural antioxidants resveratrol and pinostilbene against age-related DAergic cell death and motor dysfunction using SH-SY5Y neuroblastoma cells and young, middle-aged, and old male C57BL/6 mice. Resveratrol and pinostilbene protected SH-SY5Y cells from a DA-induced decrease in cell viability. Dietary supplementation with resveratrol and pinostilbene inhibited the decline of motor function observed with age. While DA and its metabolites (DOPAC and HVA), dopamine transporter, and tyrosine hydroxylase levels remain unchanged during aging or treatment, resveratrol and pinostilbene increased ERK1/2 activation in vitro and in vivo in an age-dependent manner. Inhibition of ERK1/2 in SH-SY5Y cells decreased the protective effects of both compounds. These data suggest that resveratrol and pinostilbene alleviate age-related motor decline via the promotion of DA neuronal survival and activation of the ERK1/2 pathways. |
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