Resveratrol and pinostilbene confer neuroprotection against aging-related deficits through an ERK1/2 dependent-mechanism

Authors: ALLEN, ERIKA - DUQUESNE UNIVERSITY; POTDAR, SNEHA - DUQUESNE UNIVERSITY; TAPIAS, VICTOR - UNIVERSITY OF PITTSBURGH; PARMAR, MAYUR - UNIVERSITY OF FLORENCE; MIZUNO, CASSIA; RIMANDO, AGNES; CAVANAUGH, JANE - DUQUESNE UNIVERSITY

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/24/2017
Publication Date: 10/24/2017
Citation: Allen, E.N., Potdar, S., Tapias, V., Parmar, M., Mizuno, C.S., Rimando, A.M., Cavanaugh, J.E. 2017. Resveratrol and pinostilbene confer neuroprotection against aging-related deficits through an ERK1/2 dependent-mechanism. Journal of Nutritional Biochemistry. 54:77-86.
DOI: https://doi.org/10.1016/j.jnutbio.2017.10.015

Interpretive Summary: 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.

Technical Abstract: Age-related declines in motor function may be due, in part, to an increase in oxidative stress in the aging brain leading to death of brain cells that transmit dopamine (DA), one of the brain chemicals responsible for transmitting signals between brain nerve cells. We examined the neuroprotective effects of the natural compounds resveratrol and pinostilbene, which are known antioxidants, both in vitro and in vivo. In in vitro studies, we used SH-SY5Y cells, which are commonly used as in vitro models of neuronal function and differentiation. Resveratrol and pinostilbene protected the cells from decrease in viability, and increased the activation ERK1 and ERK2, two widely expressed intracellular signaling protein molecules. In in vivo studies, we used young, middle-aged, and old male mice. Dietary supplementation with resveratrol and pinostilbene inhibited the decline in motor function observed with age. Resveratrol and pinostilbene also increased the activation of ERK1/2, and in an age-dependent manner. Our 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.