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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #334136
Title: Walnut extract modulates activation of microglia through alteration in 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: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/27/2017
Publication Date: 12/19/2017
Citation: Thangthaeng, N., Poulose, S., Fisher, D.R., Shukitt Hale, B. 2017. Walnut extract modulates activation of microglia through alteration in intracellular calcium concentration. Nutrition Research. 49:88-95. https://doi.org/10.1016/j.nutres.2017.10.016.
DOI: https://doi.org/10.1016/j.nutres.2017.10.016

Interpretive Summary: Previous data from our laboratory demonstrated that treatment of cultured cells with walnut extracts protects cells from death due to an inflammatory agent by promoting anti-inflammatory activities. The current study was undertaken to test whether the anti-inflammatory effects of walnut are attributed to its ability to modulate the level of calcium (an important regulator of cell function) within the cell. Using a rat brain cultured cell line as a model, treatments with walnut (1.5, 3, or 6%) induced a slow rise in intracellular calcium in a concentration- and time-dependent manner, and this rise became exaggerated when cells were chemically induced to generate an electrical signal. Cells treated with walnut were also seen to have an increase in the levels of a calcium-sensing protein, with one hour post-treatment being the peak time, regardless of walnut concentration. Additionally, treatment with walnut one hour prior to treatment with an inflammatory agent was found to be effective, not only in preventing increases in cellular inflammatory mediators, but also in reversing the levels of molecules that, as a result of inflammation, cause the cell to lose its regulation of calcium. These findings suggest that bioactive compounds in walnut are capable of modulating brain cell activation through regulating intracellular calcium. This information could lead to nutritional interventions using walnuts and possible treatment of chronic inflammation and neurodegeneration.

Technical Abstract: Previous data from our laboratory demonstrated that treatment with walnut extracts (WN) protects cells against oxidative and inflammatory cytotoxicity and promotes anti-inflammatory activities. The current study was undertaken to test whether the anti-inflammatory effects of WN are attributed to its ability to modulate intracellular calcium. Using HAPI cells, a rat microglial cell-line, as a model, treatments with WN (1.5, 3, or 6%) induced a slow rise in intracellular calcium in a concentration- and time-dependent manner, and this rise became exaggerated when cells were depolarized with potassium chloride (KCl, 100mM). Cells treated with WN (1, 3, or 6%) up-regulated calmodulin (CaM) protein levels, with one hour post-treatment being the peak time, regardless of WN concentration. Interestingly, this WN-induced up-regulation of CaM was blocked by pre-treatment with thapsigargin. Additionally, treatment with WN (1, 3, or 6%) one hour prior to lipopolysaccharides (LPS) treatment was found to be effective in preventing LPS-induced up-regulation of inducible nitric oxide synthase (iNOS) expression, up-regulation of ionized Ca2+-binding adaptor-1 (IBA-1), and down-regulation of CaM. These findings suggest that bioactive compounds in walnut are capable of modulating microglial activation through regulating intracellular calcium and CaM expression. This information could lead to nutritional interventions using walnuts and possible treatment of chronic inflammation and neurodegeneration.