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Title: Restoration of stressor-induced calcium dysregulation and autophagy inhibition by polyphenol-rich acai (Euterpe sps.) fruit pulp extracts in rodent brain cells in vitro

item Poulose, Shibu
item Fisher, Derek
item BIELINSKI, DONNA F. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item GOMES, STACY M. - University Of Cincinnati
item RIMANDO, AGNES M. - University Of Mississippi
item SCHAUSS, ALEXANDER G. - Aimbr Life Sciences
item Shukitt-Hale, Barbara

Submitted to: Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/26/2013
Publication Date: 6/8/2014
Citation: Poulose, S.M., Fisher, D.R., Bielinski, D., Gomes, S., Rimando, A., Schauss, A., Shukitt Hale, B. 2014. Restoration of stressor-induced calcium dysregulation and autophagy inhibition by polyphenol-rich acai (Euterpe sps.) fruit pulp extracts in rodent brain cells in vitro. Nutrition. 30: 853-862.

Interpretive Summary: Fruit pulp extracts of two different varieties of acai, grown largely in the Amazon delta and a popular ingredient of North American beverages, were investigated for their protective effects on brain cells grown in culture. The brain cells were subjected to normal and stressful conditions and pretreated with the pulp extracts to determine the extent of benefits. Under induced stress conditions, acai pulp extracts from both varieties were able to protect brain cells. When the cells’ natural housekeeping mechanisms were blocked, acai pulp was able to reverse the blocking caused by the toxins. This study offers new insights into the cellular mechanisms by which antioxidant-rich diets act on brain cells as well as the potential health benefits of the anthocyanin-rich acai fruits.

Technical Abstract: Oxidative damage to lipids, proteins and nucleic acids in brain often causes progressive neuronal degeneration and death which are the focal traits of chronic and acute pathologies in the brain, including those involving cognitive decline. It has been postulated that at least part of the loss of cognitive function in aging may be dependent upon a dysregulation in Ca2+ homeostasis and a loss of autophagy function in brain, which affects numerous signaling pathways as well as altered protein homeostasis. In the current study, polyphenol-rich fruit pulp extracts from two species of açaí, Euterpe precatoria (EP) and Euterpe oleracea (EO), when applied to pre-embryonic hippocampal neurons (E18), caused a significant (P<0.05) recovery of depolarized brain cells from dopamine-(DA-)induced Ca2+ influx. The polyphenol profile of EP had substantially higher concentrations of major flavonoids as compared to EO. Autophagy, a key mechanism of maintaining protein homeostasis in brain, when abolished by known inhibitors such as bafilomycinA1 or wortmannin, caused significant reduction in the growth of primary basal dendrites in rodent primary hippocampal neurons and significant accumulation of polyubiquitinated proteins in mouse HT22 hippocampal neurons in culture. However, pretreatment with açaí extracts up to 1mg/ml significantly increased the length of basal dendrites and attenuated the inhibitor-induced autophagy dysfunction. Açaí pulp extracts activated the phosphorylation of mTOR, increased the turnover of autophagosomes and MAP1B-LC3-II, and decreased accumulation of LC3-ubiquitin binding P62/SQSTM1. The relative effects were more pronounced for EP than for EO, relating to the more concentrated polyphenol profile of EP. The study adds to the growing evidence supporting the putative health effects of açaí species on brain cells.