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Title: Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in BV-2 microglial cells

Author
item Fisher, Derek
item Poulose, Shibu
item BIELINSKI, DONNA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Shukitt-Hale, Barbara

Submitted to: Nutritional Neuroscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/18/2014
Publication Date: 8/24/2014
Citation: Fisher, D.R., Poulose, S.M., Bielinski, D.F., Shukitt Hale, B. 2014. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in BV-2 microglial cells. Nutritional Neuroscience. 20(2):103-109. doi: 10.1179/1476830514Y.0000000150.

Interpretive Summary: Previous studies from our laboratory have reported that walnuts improve the age-associated declines in cognition and brain function in rats. In this study we used serum from rats that were fed a walnut diet as a pretreatment in stressed BV2 microglial cells (a brain cell derived from mice). We were able to determine that walnut diet serum (6% and 9%) significantly reduced nitrite release; a measure of inflammation, compared to untreated control cells and those treated with serum from rats fed 0% walnut diets. The results also show a decrease in pro-inflammatory factors with walnut serum used as a pretreatment. This study further asserts the protective effects of walnut metabolites on aging and also suggests antioxidant and anti-inflammatory protection or enhancement of membrane-associated functions in brain cells by walnut serum metabolites.

Technical Abstract: The shift in equilibrium towards excess reactive oxygen or nitrogen species production from innate antioxidant defenses in brain is a critical factor in the declining neural function and cognitive deficit accompanying age. Previous studies from our laboratory have reported that walnuts, rich in polyphenols, antioxidants, and omega fatty acids such as alpha linolenic acid and linoleic acid, improve the age-associated declines in cognition and neural function in rats. Possible mechanisms of action of these effects include enhancing protective signaling, altering membrane microstructures, decreasing inflammation, and preventing accumulation of polyubiquitinated protein aggregates in critical regions of the brain. In the current study, we investigated whether the serum collected from aged animals fed with walnut diets (0%, 6% and 9%, w/w) would enhance protection on stressed BV-2 microglia in vitro. In the growth medium, fetal bovine serum was substituted with the serum collected from 22 month old rats fed per protocol for 12 weeks. Walnut diet serum (6% and 9%) significantly attenuated lipopolysaccharide-induced nitrite release compared to untreated control cells and those treated with serum from rats fed 0% walnut diets. The results also indicated a significant reduction in pro-inflammatory TNF-a, COX-2 and iNOS. These results suggest antioxidant and anti-inflammatory protection or enhancement of membrane-associated functions in brain cells by walnut serum metabolites.