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Title: Walnut extracts protect cultured microglia against LPS-induced neurotoxicity via modulation of intracellular calcium concentration

Author
item Thangthaeng, Nopporn
item POULOSE, SHIBU - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Fisher, Derek
item Shukitt-Hale, Barbara

Submitted to: Society for Neuroscience Abstracts and Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 6/25/2014
Publication Date: 11/15/2014
Citation: Thangthaeng, N., Poulose, S., Fisher, D.R., Shukitt Hale, B. 2014. Walnut extracts protect cultured microglia against LPS-induced neurotoxicity via modulation of intracellular calcium concentration. Society for Neuroscience Abstracts and Proceedings. 2014. Program #144.17.

Interpretive Summary:

Technical Abstract: Walnuts are rich in omega-3 fatty acids, alpha-linolenic acid (ALA) and linoleic acid (LA), as compared to other edible plants. Previously, our laboratory had demonstrated that dietary walnut supplementation in aged animals enhanced protective signaling pathways, altered membrane microstructures, and prevented accumulation of polyubiquitinated aggregates in neurons. Furthermore, treatment with walnut extracts has been shown to protect microglia against LPS-induced cell-death and calcium dysregulation. Taken together, we hypothesized that walnut extracts protect cells against LPS-induced toxicity by modulating intracellular calcium buffering capacity and calcium signaling, which may involve flotillin-1 and platelet-activating factor receptors (PAF-R). HAPI cells, a rat microglial cell-line, treated with walnut extracts showed increased expression of calcium sensor proteins, calmodulin, and neuronal calcium sensor 1, in a concentration- and time-dependent manner. Cells treated with walnut extracts showed a slow rise in intracellular calcium which blunted further rise when depolarized by KCl. Additionally, pretreatment with walnut extracts for 8 hours reduced the concentration of flotillin-1, a lipid raft marker, in the crude membrane preparations compared to LPS-treated. These results suggest that treatment with walnut extracts protect the cells against LPS-induced toxicity by increasing intracellular calcium buffering capacity and decreasing the number of lipid rafts present at the plasma membrane, thus preventing further LPS-induced calcium flux.