|BIELINSKI, DONNA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|STEINDLER, DENNIS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|ZHENG, TONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: Current Developments in Nutrition
Publication Type: Abstract Only
Publication Acceptance Date: 2/28/2018
Publication Date: 6/28/2018
Citation: Shukitt Hale, B., Fisher, D.R., Bielinski, D.F., Steindler, D., Zheng, T. 2018. Dietary intervention with blueberries and Epidiferphane (EDP) enhances calcium buffering in rat hippocampal neurons and reduces stress signaling in microglial cells [abstract]. Current Developments in Nutrition. 2(11):nzy043.
Technical Abstract: Objectives: Age-related decrements result from increased susceptibility to and accumulating effects of oxidative stress and inflammation, as well as from dysregulation in Ca2+ homeostasis, which affects numerous signaling pathways. Some foods and their components contain bioactive phytochemicals that exhibit potent antioxidant and anti-inflammatory activities, and these foods have been shown to mitigate cognitive decline in aged animals and humans. This study investigated whether the polyphenolics from blueberries (BB) or Epidiferphane™ (EDP), a combination of phytochemicals incorporating green tea catechin (epigallocatechin gallate, EGCG), curcumin from turmeric, and broccoli sprouts which contain the isothiocyanate sulforaphane, could enhance calcium buffering in neurons and reduce stress signaling in microglial cells. Methods: Rat hippocampal neurons or HAPI microglial cells were pre-treated for a week with various concentrations of either freeze-dried BB extract, EDP, or its individual components before inducing deficits in Ca2+ buffering with dopamine (DA, 0.1uM for 2 hours) or inflammation using lipopolysaccharide (LPS, 100 ng/ml overnight), respectively. Results: BB, EDP, and EGCG were able to protect against deficits in Ca2+ buffering (both % of cells that recovered and recovery time, p < 0.05) induced by DA, showing that pre-treatment with these compounds can reduce both stress- and inflammatory- induced neuronal dysfunction. Additionally, BB, EDP, and EGCG reduced (p < 0.05) stress-mediated signaling in HAPI rat microglial cells by attenuating LPS-induced nitrite release, iNOS expression, and TNF-alpha release, but not COX-2 expression. The individual components of EDP, particularly broccoli sprouts and curcumin, were not as effective as the whole compound, showing that the individual polyphenols in the different components may be acting synergistically or exerting their effects through different and/or independent mechanisms. Conclusions: Dietary intervention with compounds such as those found in blueberry, green tea, turmeric, or broccoli sprouts can play a role in reducing the age-related CNS inflammation, microglial activation, dysregulation in Ca2+ homeostasis, and stimulation of immune pathways that reduce neurogenesis and impair cognitive function.