ARS | Publication request: Differential protection among fractionated blueberry polyphenolic families against DA-, ABeta 42 and LPS-induced decrements in Ca2+ buffering in primary hippocampal cells

Submitted to: Journal of Agriculture and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 17, 2010
Publication Date: July 28, 2010
Citation: Joseph, J.A., Shukitt Hale, B., Brewer, G.J., Weikel, K.A., Kalt, W., Fisher, D.R. 2010. Differential protection among fractionated blueberry polyphenolic families against DA-, ABeta 42 and LPS-induced decrements in Ca2+ buffering in primary hippocampal cells. Journal of Agriculture and Food Chemistry. 58:8196-8204.

Interpretive Summary: It has been theorized that at least part of the loss of brain function in aging may be the results of decreases in calcium recovery and increased inflammatory stress signals. However, previous research showed that aged animals supplemented with blueberry extract showed a better calcium recovery and fewer motor and memory deficits. A recent subsequent experiment has shown that stressor-induced deficits in calcium recovery in brain cells were prevented by blueberry extract, and inflammatory signals were reduced. Present experiments determined the most effective blueberry component fraction that could protect against these inflammation-induced deficits. Brain cells treated with blueberry extract, partial fractions, or control medium were exposed to 3 different stressors. Results indicated that the degree of protection against deficits in calcium recovery varied as a function of the stressor. The whole blueberry, as well as 2 particular fractions, offered the greatest protection. Protective capabilities of the various fractions depended upon the stressor. The viability data indicated that the whole blueberry and one of the fractions showed greater protection against the stressors than the more fractionated components. Thus, these results suggest that, except for a few instances, the more complete the blueberry fraction, the greater the effects – especially with respect to prevention of inflammation and stress signal generation and viability.

Technical Abstract: It has been postulated that at least part of the loss of cognitive function in aging may be the result of deficits in Ca2+ recovery (CAR) and increased oxidative/inflammatory (OX/INF) stress signaling. However, previous research showed that aged animals supplemented with blueberry (BB) extract, showed fewer deficits in CAR, as well as motor and cognitive functional deficits. A recent subsequent experiment has shown that DA- or ABeta42-induced deficits in CAR in primary hippocampal neuronal cells (HNC) were antagonized by BB extract, and (OX/INF) signaling was reduced. Present experiments assessed the most effective BB polyphenol fraction that could protect against OX/INF-induced deficits in CAR, ROS generation, or viability. HNCs treated with BB extract, BB fractions (e.g., proanthocyanidin, PAC), or control medium were exposed to dopamine (DA, 0.1mM), amyloid beta (ABeta42, 25 uM) or lipopolysaccharide (LPS, 1ug/ml). Results indicated that the degree of protection against deficits in CAR varied as a function of the stressor and was generally greater against ABeta42 and LPS than DA. The whole BB, anthocyanin (ANTH) and pre-C18 fractions offered the greatest protection, while chlorogenic acid offered the lowest protection. Protective capabilities of the various fractions against ROS depended upon the stressor, where the BB extract and the combined PAC (high and low m.w.) fraction offered the best protection against LPS and ABeta42 but were less effective against DA-induced ROS. The high and low m.w. PACs and the ANTH fractions enhanced ROS production regardless of the stressor used and this reflected increased activation of stress signals (e.g., P38 MAPK). The viability data indicated that the whole BB and combined PAC fraction showed greater protective effects against the stressors than the more fractionated polyphenolic components. Thus, these results suggest that, except for a few instances, the lesser the polyphenolic fractionation the greater the effects, especially with respect to prevention of ROS and stress signal generation, and viability.